Audio Journal of Oncology Podcast

Amir Fathi MD; ASH 2025: Paradigm Study Finds Young, Fit Adults with Acute Myeloid Leukemia Do Better with Gentler Azacitidine/Venetoclax Initial Therapy An interview with: Amir Fathi MD, Leukemia Program Director, Massachusetts General Hospital and Associate Professor of Medicine, Harvard Medical School, Boston, USA. ORLANDO, USA— Young, fit adults with acute myeloid leukemia had fewer toxicities and better response rates when treated with a combination of venetoclax plus azacytidine in comparison with similar group of patients who had standard induction chemotherapy. This was in the Paradigm phase two multi center randomized study reported at the 2025 Annual Meeting of the American Society of Hematology by Amir Fathi MD, the Leukemia Program Director at the Massachusetts General Hospital in Boston and Associate Professor of Medicine at Harvard Medical School, Boston, USA. At the conference he met up with Audio Journal of Oncology reporter Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Amir Fathi MD IN: [GOODWIN] “Peter Goodwin here at the American Society ….. OUT: ………of Oncology, I’m Peter Goodwin.” 10:01 secs LINK: https://ashpublications.org/blood/article/146/Supplement%201/6/553639/Results-from-paradigm-a-phase-2-randomized-multi American Society of Hematology 2025 Annual Meeting ABSTRACT 6 Results from paradigm – a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia AUTHORS: Amir Fathi, Alexander Perl, Geoffrey Fell, Brian Jonas, Brittany Ragon, Alice Mims, Uma Borate, Gabriel Mannis, Karen Quillen, Max Stahl, Paul Koller, Andrew Artz, Monzr M. Al Malki, Guido Marcucci, Mary Linton Peters, Timothy Graubert, Peter Westervelt, Philip Amrein, Hanno Hock, Andrew Brunner, Gabriela Hobbs, Rupa Narayan, Michelle Lee, Brandon Aubrey, Alyssa Watson, Richard Hao, Shilton Dhaver, Michael Grunwald, Yi-Bin Chen, Andrew Matthews, Christopher Hourigan, Brent Wood, Donna Neuberg, Areej El-Jawahri, Ibrahim Aldoss INSTITUTIONS: 1 Massachusetts General Hospital / Harvard Medical School, Boston, MA, United States, 2 Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States, 3 Dana Farber Cancer Institute, Boston, MA, United States, 4 University of California Davis Comprehensive Cancer Center, Sacramento, CA, United States, 5 Levine Cancer Institute, Atrium Health, Charlotte, NC, United States, 6 The Ohio State University, Columbus, OH, United States, 7 Stanford University School of Medicine, Stanford, CA, United States, 8 Beth Israel Deaconess Medical Center, Boston, MA, United States, 9 Yale School of Medicine, New Haven, CT, United States, 10 City of Hope, Duarte, CA, United States, 11 Massachusetts General Hospital, Boston, MA, United States, 12 MaineHealth, Brunswick, ME, United States, 13 Fralin biomedical research institute, Virgina Tech University, Roanoke, VA, United States, 14 Children’s Hospital Los Angeles, University of Southern California, Los Angeles, MA, United States Introduction: For decades, standard upfront treatment for acute myeloid leukemia (AML) among fit patients (pts) has been intensive induction chemotherapy (IC), typically with cytarabine and anthracyclines. However, long-term outcomes remain poor, and IC continues to pose substantial short- and long-term morbidities, with significant burden to pts and hospitals. VIALE-A, a phase 3 trial of IC-ineligible pts, established superiority of azacitidine and venetoclax (aza-ven) vs aza alone, with a median OS of 15 months and composite remission rate (CCR) of 66%, which compare favorably to that expected for IC among older pts. We prospectively tested whether aza-ven was superior to IC in fit pts and could challenge the current treatment standard. Methods: This open-label, multicenter, phase II randomized clinical trial compared the therapeutic activity of conventional IC (7+3 regimen or liposomal daunorubicin and cytarabine [CPX351]) to aza-ven among IC-eligible pts aged ≥ 18. Pts with core binding factor fusions, FLT3 mutations, or NPM1 mutations (unless aged ≥ 60) were excluded. The IC arm incorporated cycles of chemotherapy consolidation following induction, for use as clinically appropriate per current standard of care. Pts were allowed to proceed to transplant (HCT) on both arms following response on protocol-directed therapy. The primary endpoint was event free survival (EFS), with events defined as progressive disease, persistent disease prompting therapy change, relapse, hospice, or death. Among secondary endpoints were response rates, OS, toxicity, measurable residual disease (MRD), hospitalization metrics, and quality of life (QOL). Pts were stratified by age (≥ 65 vs < 65) and pre-randomization selection in the IC arm to 7+3 or CPX351. EFS is estimated by Kaplan Meier method and assessed by log rank test and Cox PH regression. Clinical responses are assessed using an exact binomial tes

Jennifer A. Woyach MD, ASH 2024: The Non-Covalent Bruton’s Tyrosine Kinase-Inhibitor Pirtobrutinib is As Effective, While Less Toxic, In Relapsed/Refractory Chronic Lymphocytic Leukemia An interview with: Jennifer A. Woyach MD, Director of Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States ORLANDO, USA—The possibility of using a less toxic Bruton’s tyrosine kinase (BTK) inhibitor to treat chronic lymphocytic leukemia/small lymphocytic lymphoma—especially in treatment naïve patients— could become a reality according to promising findings from the first randomized phase III study comparing a non-covalent with a covalent BTK inhibitor. Study findings were announced at the American Society of Hematology 2025 Annual Meeting by Jennifer A. Woyach MD, Director of the Division of Hematology at the Ohio State University Comprehensive Cancer Center in Columbus, USA. After her talk at the conference Dr. Woyach discussed the data with the Audio Journal of Oncology’s Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Jennifer Woyach MD IN: [GOODWIN]“Peter Goodwin here in Orlando Florida …. OUT: ….in Orlando Florida, I’m Peter Goodwin. 5:39 secs PUBLICATION REFERENCE: https://ashpublications.org/blood/article/146/Supplement%201/683/551183/Pirtobrutinib-vs-ibrutinib-in-treatment-naive-and Blood (2025) 146 (Supplement 1): 683. https://doi.org/10.1182/blood-2025-683 TITLE: Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor Jennifer Woyach, Lugui Qiu, Sebastian Grosicki, Tomasz Wrobel, Marcelo Capra, Jaroslaw Czyz, Shuhua Yi, Ki-Seong Eom, Anna Panovská, Wojciech Jurczak, Kamel Laribi, Lutz Jacobasch, Ross Baker, Richy Agajanian, Alejandro Berkovits, Muhit Özcan, Stephane Lepretre, Catherine Coombs, Paula Cramer, Katharine Lewis, Marisa Hill, Katherine Bao, Yuanyuan Bian, Amy Ruppert Stark, Ching Ching Leow, William Wierda 2025 ASH Orlando, Abstract: 683 Abstract Title : Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor Category: 600s – Hematologic Malignancy Review Category: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological Lead Author: Jennifer A. Woyach MD, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States Institutions: 1 The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States, 2 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China, 3 Medical University of Silesia, Department of Cancer Prevention, Katowice, Poland, 4 Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wroclaw, Wroclaw, Poland, 5 Centro Integrado de Hematologia e Oncologia, Hospital Mãe de Deus, Porto Alegre, Brazil, 6 Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Departament of Hematology, Bydgoszcz, Torun, Poland, 7 Department of Hematology, Catholic Hematology Hospital, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, Rep. of South, 8 Department of Internal Medicine -Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic, 9 Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland, 10 Department of Hematology, Centre Hospitalier Le Mans, Le Mans, France, 11 Praxis of Haematology and Oncology, Dresden, Germany, 12 Western Australia Centre for Thrombosis and Haemostasis, Perth Blood Institute, Murdoch University, Perth, Australia, 13 The Oncology Institute of Hope and Innovation, Whittier, CA, United States, 14 Inmunocel, Santiago, Chile, 15 Ankara University, School of Medicine, Ankara, Türkiye, 16 Centre de Lutte Contre le Cancer – Centre Henri Becquerel, Rouen, France, 17 University of California Irvine, Irvine, CA, United States, 18 Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German Chronic Lymphocytic Leukemia Study Group, University of Cologne, Cologne, Germany, 19 Sir Charles Gairdner Hospital, Division of Haematology, Nedlands, Western Australia, Australia, 20 Medical School, University of Western Australia, Division of Internal Medicine, Perth, Western Australia, Australia, 21 Eli Lilly and Company, Indianapolis, United States, 22 University of Texas MD Anderson Cancer Center, Houston, TX, Abstract: Introduction: Covalent Bruton tyrosine kinase inhibitors (cBTKi) are a mainstay of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)

Alexis Ann LeVee MD; 2025 SABCS: Pre-Operative Gut Microbiome Predicts Complete Response to Immune Checkpoint Inhibition in Patients with Early-stage HER2-positive Breast Cancer An interview with: Alexis Ann LeVee MD, Clinical Instructor of Medicine, UCLA David Geffen School of Medicine, Los Angeles, USA. SAN ANTONIO, USA—New evidence that what patients eat can have a strong influence on the effectiveness of their cancer treatment was illustrated by new research on the microbiome reported at the 2025 San Antonio Breast Cancer Symposium. The conference saw results from the randomized phase II neoHIP trial looking at microbiome bacterial profiles in patients with HER2-positive early breast cancer at a poster from Alexis LeVee MD of the UCLA David Geffen School of Medicine in Los Angeles. During the session she talked about the results with Audio Journal of Oncology reporter, Peter Goodwin: POSTER TITLE Gut microbiome composition predicts pathologic complete response in patients with early-stage HER2-positive breast cancer receiving neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab SPEAKER: Alexis LeVee, UCLA David Geffen School of Medicine, Los Angeles, CA AUTHORS: LeVee1, K. Lee2, S. Rice3, I. Chan3, S. Sridharan3, S. Shiao4, S. Pal5, H. McArthur3; 1Department of Medicine, Division of Hematology and Oncology, UCLA David Geffen School of Medicine, Los Angeles, CA, 2TGen Integrated Microbiomics Center (TIMC), Translational Genomics Research Institute (TGen), Flagstaff, AZ, 3Department of Medicine, Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX, 4Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 5Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA. Background: The gut microbiome has been shown to influence response to immune checkpoint inhibitors (ICI). This study aimed to investigate the association between gut microbiome profiles and clinical outcomes in patients with early-stage HER2-positive (HER2+) breast cancer receiving neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (K) as part of the randomized phase II neoHIP trial. Methods: Patients with stage II-III HER2+ breast cancer were randomized to 3 treatment arms: Arm A consisted of paclitaxel (T), trastuzumab (H), and pertuzumab (P), THP; Arm B of THP-K; and Arm C of TH-K. Fecal samples were collected at baseline, cycle 3 day 1, surgery, and at 30 and 60 days post-surgery and were analyzed using deep shotgun metagenomics sequencing. Pre-operative fecal samples were analyzed according to pathologic complete response (pCR) and onset of diarrhea during the neoadjuvant period. Comparisons were adjusted to control for false discovery rates (q-value). Results: 99 fecal samples (Arm A: n=32; Arm B: n=48; Arm C: n=19) from 27 patients were included in the analysis. Bacterial diversity by Jaccard analysis was significantly different across all time points for all arms (all p<0.05; q<0.05). In the THP and THP-K arms, Jaccard analysis demonstrated differences in gut microbiome diversity in patients who achieved pCR versus non-pCR (p=0.009; q=0.009). In patients treated with THP who achieved pCR, multiple species were in greater abundance including GGB9237 SGB14179 (log fold change [LFC] 6.87), GGB34797 SGB14322 (LFC 6.25), and Faecalicatena fissicatena (LFC 4.61) compared to those with non-pCR (all p<1E-5; q<0.01). In the THP-K arm, patients who achieved pCR had different species in greater abundance, including GGB9365 SGB14341 (LFC 3.15), Hydrogenoanaerobacterium saccharovorans (LFC 2.92), and GGB9502 SGB14899 (LFC 2.56) compared to those with non-pCR (all p<0.0001; q<0.01). Comparing those who achieved pCR in THP vs. THP-K, GGB9715 SGB15260 (LFC 4.89), Brotolimicola acetigignens (LFC 4.88), and Clostridiaceae bacterium Marseille Q4149 (LFC 4.54) were higher in abundance in the THP-K arm, and GGB34797 SGB14322 (LFC 6.27) and GGB3175 SGB4191 (LFC 5.73) were depleted in the THP-K arm (all p<0.0001; q<0.05). In patients with diarrhea vs. without diarrhea, beta diversity was significantly different in the THP arm by Bray Curtis analysis (p<0.05; q<0.05) and in the THP-K arm by Jaccard analysis (p<0.05; q<0.05), with multiple species in different abundances in those with and without diarrhea in both arms (p<0.05). Conclusion: This is the first study to demonstrate that the pre-operative gut microbiome influences response to ICI in patients with early-stage HER2+ breast cancer. Patients who achieved pCR had a significantly different microbiome profile compared to those with residual disease. This study highlights the role of the gut microbiome in influencing response to ICI in patients with breast cancer treated in the curative intent setting. Alexis Ann LeVee 2025 SABCS AJOncology

B-Cell Maturation Antigen Bispecific Antibody Linvoseltamab Brings High Response Rates in Patients with Relapsed/Refractory Multiple Myeloma An interview with: Meletios-Athanasios C. Dimopoulos MD, Professor and Chair, Department of Clinical Therapeutics (Alexandra Hospital), School of Medicine, University of Athens, Greece. ORLANDO, USA—The bispecific monoclonal antibody linvoseltamab achieved high rates of clinical response when used in combination with anti-CD 38 therapy in patients who had relapsed/refractory multiple myeloma. Early findings on efficacy and safety from the phase 1b LINKER-MM2 trial were announced at the 2025 Annual Meeting of the American Society of Hematology by Meletios Dimopoulos MD, Chair of Clinical Therapeutics at the University of Athens in Greece. Peter Goodwin caught up with him just after his talk: Audio Journal of Oncology: Meletios-Athanasios C. Dimopoulos MD IN: [GOODWIN]I am here at the American…. OUT: ….. Journal of Oncology, I’m Peter Goodwin. 8:20 secs 2025 ASH Abstract 2254 Safety and efficacy of linvoseltamab (LINVO) combined with anti-CD38 monoclonal antibodies (mAbs) daratumumab (DARA) or isatuximab (ISA) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the multicohort, Phase 1b LINKER-MM2 trial ASH ABSTRACT: 2254 Title : “Safety and efficacy of linvoseltamab (LINVO) combined with anti-CD38 monoclonal antibodies (mAbs) daratumumab (DARA) or isatuximab (ISA) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the multicohort, Phase 1b LINKER-MM2 trial” Poster Abstract Session, Speaker: Meletios Dimopoulos, MD Authors Meletios Dimopoulos 1, Sosana Delimpasi2, Salomon Manier3, Jean-Marie Michot4, Enrique Ocio5, Samuel Rubinstein6, Joselle Cook7, Maria Del Carmen Martinez Chamorro8, Aurora Breazna9, Amishi Dhadwal9,Yogita Ghodke9, Sheila Masinde9, Glenn Kroog9, Shawn Sarkaria9, Albert Oriol10 Institutions: 1 Alexandra General Hospital, National and Kapodistrian University of Athens, Athens, Greece, 2Department of Hematology and Bone Marrow Transplantation Unit, General Hospital Evangelismos, Athens, Greece, 3 Hematology Department, Lille University Hospital, Lille, France, 4 Gustave Roussy Cancer Campus, Villejuif, France, 5 Servicio de Hematología y Hemoterapia, Hospital Universitario Marqués de Valdecilla University Hospital (IDIVAL) Universidad de Cantabria Santander, Santander, Spain, 6 Department of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, United States, 7 Mayo Clinic, Rochester, MN, United States, 8 Hematology Department, Hospital Universitario Quirónsalud Madrid and Universidad Europea de Madrid, Madrid, Spain, 9 Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States, 10 Department of Hematology, Institut Català d’Oncologia i Institut Josep Carreras Hospital Germans Trias i Pujol, Badalona, Spain Phase 1b LINKER-MM2 trial (NCT05137054). Introduction LINVO, a human B-cell maturation antigen (BCMA)xCD3 bispecific antibody, was recently approved for triple-class exposed (TCE) RRMM after ≥3 prior therapies (EU) or ≥4 prior lines of therapy (US), demonstrating high efficacy and a generally manageable safety profile. Combining LINVO with an anti-CD38 mAb, such as DARA or ISA, may provide additional benefit to pts with RRMM. Here we report pooled safety and efficacy results from the LINVO + DARA and LINVO + ISA cohorts during the dose-finding portion of the Phase 1b LINKER-MM2 trial (NCT05137054). Methods Eligible pts were aged ≥18 years with RRMM that progressed after ≥3 lines of therapy (LoTs), or ≥2 LoTs if TCE or double-class refractory (immunomodulatory drug [IMiD] + proteasome inhibitor [PI]). Prior treatment (tx) with DARA or ISA was allowed if previously tolerated and ≥6 months (mos) or ≥3 mos washout, respectively, had elapsed since last exposure. Tx began with LINVO monotherapy (Cycle [C]0; 28-day cycle) consisting of 2 step-up doses (5 mg, 25 mg) and 2 full doses (dose level [DL]1 100 mg; DL1b 150 mg; DL2 200 mg) before standard dosing of DARA or ISA was added at C1. LINVO was given once weekly in C1–3 and once every 2 weeks in C4+. At the end of 2024, dosing once every 4 weeks was implemented after C6 if a very good partial response or better (≥VGPR) was achieved. Dexamethasone premedication was required during the first 2 cycles and then given per label for DARA or ISA. Primary endpoints: dose-limiting toxicities (DLTs) and tx-emergent adverse events (TEAEs). Key secondary endpoints: overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and rate of minimal residual disease (MRD) negativity. The analyses reported here combine the LINVO + DARA and LINVO + ISA cohorts. Results As of May 7, 2025, 42 pts were enrolled. All pts were included in the safety analysis set: DL1 (DARA, n=12; ISA, n=6), DL1b (n=6; n=10), or DL2 (n=8; n=0); 37 were included in the efficacy analysis set: DL1 (DARA, n=11; ISA, n=5), DL1b (

Antonio Jimenez Jimenez MD MS; ASH 2025: Donor Choice No Longer a Barrier to Allogeneic Stem Cell Transplantation for Patients with Hematologic Malignancies An interview with: Antonio Jimenez Jimenez MD MS, Associate Professor of Medicine, Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Sylvester Cancer Center, Co-Chair National Marrow Donor Program Access Trial, Miami, FL, United States ORLANDO, USA—A wider, more ethnically diverse range of patients could safely receive allogeneic hematopoietic cell transplantations from unrelated donors according to findings from the USA-based National Marrow Donor Program Access Trial reported at the 2025 Annual Meeting of the American Society of Hematology. The use of post-transplant cyclophosphamide appears to be levelling the playing field for patients who do not have access to a fully matched donor, according to Antonio Jimenez Jimenez MD MS, from the University of Miami Miller School of Medicine, who co-chairs the National Marrow Donor Program Access Trial. After telling the conference about his new data he gave the details to the Audio Journal of Oncology’s Peter Goodwin: Audio Journal of Oncology: Antonio Jimenez Jimenez MD MS IN [GOODWIN]”Here from the American Society of …. OUT: …..I’m Peter Goodwin 10:58secs REFERENCE: https://ashpublications.org/blood/article/146/Supplement%201/936/552282/Mismatching-of-unrelated-donors-beyond-a-single ASH 2025 Abstract Number: 936 ABSTRACT TITLE : Mismatching of unrelated donors beyond a single HLA-locus does not adversely impact outcomes at one year following transplantation: Results from the NMDP sponsored ACCESS study (Category: 700s – Transplantation and Adoptive Cell Therapies Review Category: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution) AUTHORS Monzr M. Al Malki1, Stephanie Bo-Subait2, Brent Logan3, 4, Sarah Smith2, Erin Leckrone2, Heather Stefanski2, Jeffery Auletta2, Stephen Spellman2, Craig Malmberg2, Medhat Askar2, 5, Rachel Cusatis4, Brian Shaffer6, Dipenkumar Modi7, Farhad Khimani8, Mahasweta Gooptu9, Mehdi Hamadani4, Martin Maiers2, Joseph Stanek2, Javier Meade10, Uttam Rao11, Jordan Milner12, Ramzi Abboud13, Katarzyna Jamieson14, George Carrum15, Bhagirathbhai Dholaria16, William Hogan17, Ran Reshef18, Satyajit Kosuri19, Rachel Cook20, Karen Ballen21, Alison Loren22, Karilyn Larkin23, Sally Arai24, Muna Qayed25, Sung Choi26, Larisa Broglie4, 27, Bronwen Shaw4, Steven Devine2, Antonio Jimenez Jimenez28 INSTITUTIONS: 1 City of Hope National Medical Center, Duarte, CA, United States, 2 CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN, United States, 3 Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI, United States, 4 CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI, United States, 5 Health Sector & College of Medicine, Qatar University, Doha, Qatar, 6 Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 7 Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States, 8 Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, United States, 9 Department of Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, United States, 10 Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Boston, MA, United States, 11 Sarah Cannon Transplant and Cellular Therapy Program at St. David’s South Austin Medical Center, Austin, TX, United States, 12 Shands HealthCare & University of Florida, Gainesville, FL, United States, 13 Washington University in St. Louis School of Medicine, St. Louis, United States, 14 University of North Carolina Hospitals, Chapel Hill, NC, United States, 15 Baylor College of Medicine Center for Cell and Gene Therapy, Baylor College of Medicine-Methodist Hospital, Houston, TX, United States, 16 Vanderbilt University Medical Center, Nashville, TN, United States, 17 Division of Hematology/BMT, Mayo Clinic, Rochester, MN, United States, 18 Blood and Marrow Transplant and Cell Therapy Program, Columbia University Irving Medical Center, New York, NY, United States, 19 University of Chicago Medicine, Chicago, IL, United States, 20 Knight Cancer Institute, Oregon Health & Science University, Portland, MN, United States, 21 Division of Hematology/Oncology, University of Virginia Health, Charlottesville, VA, United States, 22 Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 23 The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States, 24 Stanford Health Care, Palo Alto, CA, United States, 25 Aflac Cancer and

Safna Naozer Virji MBBS FPBS; 2025 SABCS: Oncoplastic Breast Cancer Surgery Study Reports High Efficacy with Superior Psychosocial Outcomes in a Low or Middle Income Country Setting An interview with: Safna Naozer Virji MBBS FPBS Breast Surgery Fellow, Aga Khan University Hospital, Karachi , Pakistan SAN ANTONIO, USA—Breast cancer surgeons can deliver high levels of satisfaction to worried patients without sacrificing efficacy in resource-limited settings in a low or middle income country, according to research from Pakistan reported at the 2025 San Antonio Breast Cancer Symposium. Safna Naozer Virji MBBS FPBS, who is a Breast Surgery Fellow at the Aga Khan University Hospital in Karachi, Pakistan, gave a poster presentation at the conference reporting the outcome of a large series of procedures conducted at her center. Audio Journal of Oncology reporter Peter Goodwin caught up with her at her poster to find out more: Audio Journal of Oncology: Safna Naozer Virji MBBS FPBS IN: [Goodwin] “I’m talking now to … OUT: ……Journal of Oncology. I’m Peter Goodwin 7: 58” Source: Poster Session 2, Day 2: December 10, 2025, San Antonio Breast Cancer Symposium Presentation number: PS2-03-04 TITLE: Re-defining Breast Cancer care in an LMIC- a single center study on long term oncological and cosmetic outcomes of Oncoplastic Breast Surgery SPEAKER: Safna Naozer Virji, Aga Khan University Hospital, Karachi, Karachi, Pakistan AUTHORS: N. Virji, L. Vohra, S. Khan, I. Khan; Breast Surgery, Department of Surgery, Aga Khan University Hospital, Karachi, Karachi, PAKISTAN. Background: Surgical management has greatly evolved from a radical mastectomy to the most recent advancement of a more conservative oncoplastic breast surgery (OBS). It has not only proven to be safe, but also has shown superior cosmetic outcomes compared to standard breast conservation surgery as it is able to address larger and even multi-focal tumors. Nevertheless, this is a relatively novel concept in our developing country with a limited number of professionals trained in the field. Furthermore, there is a financial aspect and stigma to take into consideration. Patients have to pay out of pocket for treatment which deters them from risking the possibility of a second surgery – in case of incomplete resection margins. It also adds the burden on the surgeon to deliver optimal cosmetic outcomes with no intervention to the contralateral breast. The purpose of this study is to determine the long-term oncological and cosmetic outcomes of patients with early-stage breast cancer who underwent OBS at our institution. Methodology: A single-center retrospective study was conducted on adult female patients with biopsy proven Stage I to III breast cancer who underwent OBS from January 2017 to June, 2022. Patients who underwent bilateral breast surgery were excluded. A total of 194 women were eligible for the study and data was extracted from patient records to determine the long term oncologic outcomes— breast cancer recurrence, disease-free survival (DFS), and overall survival (OS). Cosmetic outcomes were evaluated via patient-reported satisfaction using the Harvard breast cosmesis scale, through telephonic interview after obtaining informed verbal consent. The study was approved by the institutional Ethical Review Committee (ERC 2025-11482-34955). Results: The mean age of women at diagnosis was 48.3 ± 13.2 years with 81% having invasive ductal carcinoma. Sixty-seven percent of the women had hormone receptor positive breast cancer, while 20% had triple negative disease. Among all the patients who were included in the study, half of the patients received neoadjuvant chemotherapy before OBS, followed by adjuvant radiation therapy. Of note, only 6 (3.1%) out of 194 women had a positive margin for which they underwent a second procedure. Level 1 OBS was performed among 77% of the patients. Among those who underwent Level 2 OBS a variety of local perforator flaps were performed. We had a 68% response rate among the patients who were approached via telephone to determine the self-reported cosmetic outcomes, with 91% of the participants reporting ‘Good’ (51%) or ‘Excellent’ (40%) cosmetic outcomes when compared to the contralateral breast. Eight (4.1%) out of 16 patients had an ipsilateral recurrence, while the remaining developed distant metastases. The Kaplan Meier analysis showed that the mean OS of the study participants was 96 months (95% CI=92.2-99.7) since diagnosis, with death as the outcome event. The mean DFS was 93 months (95% CI=89.5 – 97.6) since diagnosis until recurrence as the outcome event. There were significant differences in survival times for patients by recurrence (log rank test, p=0.000) and hormone receptor status (log rank test, p=0.015). There was no significant difference in survival times for patients by type of OBS (log rank test, p=0.860). Conclusion: Oncoplastic breast surgery is a safe and effective option for early-stage breast cancer, with low

Luciano Costa, MD, PhD; ASH 2025: CAR T Cell Brings Profound Benefit with Long-Term Progression-Free Survival in Patients with Standard-Risk Relapsed/Refractory Multiple Myeloma An interview with: Luciano Costa, MD PhD, University of Alabama at Birmingham, Birmingham, Alabama, United States ORLANDO, USA—The CARTITUDE-4 study has f0und that patients with standard-risk relapsed or refractory multiple myeloma can benefit greatly from ciltacabtagene autoleucel CAR-T cell therapy after one to three prior lines of therapy, as do those with high-risk disease. Study findings were reported at the American Society of Hematology 2025 Annual Meeting in Orlando Florida by Luciano Costa, MD, PhD, University of Alabama, in Birmingham, Alabama, USA. After his talk at the conference he discussed the findings with the Audio Journal of Oncology reporter, Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Luciano Costa MD PhD IN: [Goodwin] “I’m right here at the …… OUT: …. In Orlando, Florida. 13:04 secs JOURNAL ARTICLE: Reference: Blood: Volume 146, Supplement 1, 3 November 2025, Page 94 LINK: https://www.sciencedirect.com/science/article/pii/S0006497125026692 TITLE: Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed / refractory multiple myeloma First author: Luciano Costa Authors: University of Alabama at Birmingham, Birmingham, United StatesLuciano Costa 1, Albert Oriol 2, Dominik Dytfeld 3, Salomon Manier 4, Peter Voorhees 5, Yi Lin 6, Myo Htut 7, Wilfried Roeloffzen 8, Phoebe Joy Ho 9, Urvi Shah 10, Man Zhao 11, Quanlin Li 12, Agnes Balogh 13, Katherine Li 14, Ana Slaughter 15, Nina Benachour 13, Carolina Lonardi 16, Arnab Ghosh 17, Huabin Sun 17, Nikoletta Lendvai 17, Tamar Lengil 17, Nitin Patel 18, Mythili Koneru 18, Erika Florendo 18, Octavio Costa 18, Vrinda Mahajan 18, Paula Rodriguez Otero 19, Christopher Strouse 20, Keith Stewart 21, Surbhi Sidana 22 Institutions: 1.University of Alabama at Birmingham, Birmingham, United States 2Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain 3Poznan University of Medical Sciences, Poznań, Poland 4University of Lille, CHU Lille, Lille, France 5Atrium Health/Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, United States 6Mayo Clinic, Rochester, United States 7Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, United States 8Department of Hematology, University Medical Center Groningen, Groningen, Netherlands 9Royal Prince Alfred Hospital, Sydney, Australia 10Myeloma Service, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, United States 11IQVIA, Shanghai, China 12Johnson & Johnson, Apex, United States 13Johnson & Johnson, Beerse, Belgium 14Johnson & Johnson, Spring House, United States 15Johnson & Johnson, Zug, Switzerland 16Johnson & Johnson, Buenos Aires, Argentina 17Johnson & Johnson, Raritan, United States 18Legend Biotech USA Inc, Somerset, United States 19Cancer Center Clínica Universidad de Navarra, Cima, Pamplona, Spain 20Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, United States 21University Health Network and the Princess Margaret Cancer Centre, Toronto, ON, Canada 22Stanford University School of Medicine, Stanford, United States ASH Abstract Presentation ID 94 Introduction: The CARTITUDE-4 study (NCT04181827), which enrolled patients with lenalidomide-refractory multiple myeloma (MM) after 1–3 prior lines of therapy (pLOT), demonstrated a significant benefit of ciltacabtagene autoleucel (cilta-cel) over established triplet regimens. However, the benefit of cilta-cel for patients with standard-risk cytogenetics remains less defined. Here, we report outcomes in patients with standard-risk cytogenetics from the intent-to-treat and as-treated populations in CARTITUDE-4. Methods: InCARTITUDE-4, patients randomized to the cilta-cel arm underwent apheresis and bridging treatment with either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd), followed by lymphodepletion therapy with cyclophosphamide and fludarabine, and then a single cilta-cel infusion. Progression-free survival (PFS) was assessed using a validated computerized algorithm. The intent-to-treat population included 208 patients; 32 patients progressed or died on bridging therapy, resulting in an as-treated population of 176 patients. Patients with high-risk cytogenetics, defined as del(17p), t(14;16), t(4;14), gain/amp(1q) (n=105), or with unknown cytogenetics (n=12), were excluded from the as-treated analysis. The 12-month minimal residual disease (MRD)-negative complete response (CR) was defined per the International Myeloma Working Group criteria as the proportion of participants with CR or better prior to and at 12 months (±3 months), achieving MRD

Matteo Lambertini MD PhD; San Antonio Breast Cancer Symposium: ALTTO Trial Shows Adjuvant Aromatase Inhibitors Outperform Tamoxifen in Patients with ER-Positive, HER2-Positive Early Breast Cancer An interview with: Matteo Lambertini MD PhD, Assistant Professor, University of Genoa, Consultant in Medical Oncology, San Martino IST Hospital, Genoa, Italy. SAN ANTONIO, USA­—Patients with hormone receptor positive HER2-positive early breast cancer had superior outcomes when treated with aromatase inhibitor adjuvant therapy than similar patients treated with adjuvant tamoxifen or other selective estrogen receptor modulators (SERMs). This is the headline finding from a long-term analysis of the large international ALTTO trial reported at the 2025 San Antonio Breast Cancer Symposium by Matteo Lambertini MD PhD, Assistant Professor at the University of Genoa, and Consultant in Medical Oncology, San Martino IST Hospital in Genoa, Italy. After his talk at the conference he discussed the findings with the Audio Journal of Oncology’s Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Matteo Lambertini MD PhD IN: [GOODWIN] “Matteo Lambertini I am with you here at the San …….. OUT: ……for the Audio Journal of Oncology, I’m Peter Goodwin. 7:05 secs CONFERENCE DETAILS: 2025 San Antonio Breast Cancer Symposium, San Antonio, Texas USA ORAL SESSION: GS1-03 “Adjuvant aromatase inhibitor or tamoxifen in patients with hormone receptor-positive/HER2-positive early breast cancer: An exploratory analysis from the ALTTO (BIG 2-06) trial” SPEAKER: Matteo Lambertini, University of Genova – IRCCS Ospedale Policlinico San Martino, Genoa, Italy AUTHORS: Lambertini1, F. Samy2, E. Agostinetto3, L. Arecco4, P. Freire5, A. Sonnenblick6, G. Arpino7, L. Del Mastro8, A. Choudhury9, N. Harbeck10, I. Vaz-Luis11, V. Kaklamani12, A. Wolff13, A. Partridge14, S. Loi15, S. Fielding16, M. Piccart17, S. Di Cosimo18, E. de Azambuja17; INSTITUTIONS: 1Medical Oncology, University of Genova – IRCCS Ospedale Policlinico San Martino, Genoa, ITALY, 2Statistics, Frontier Science Scotland, Kingussie, UNITED KINGDOM, 3Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 4Oncology, Department of Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 5Medical Oncology, Oncologia D’Or Hospital de Câncer de Pernambuco, Recife, BRAZIL, 6Medical Oncology, The Oncology Division, Tel Aviv Sourasky Medical Center, Grey Faculty of Medicine, Tel Aviv University, Tel Aviv, ISRAEL, 7Medical Oncology, Università di Napoli Federico II, Naples, ITALY, 8Medical Oncology, University of Genova – IRCCS Ospedale Policlinico San Martino, Genova, ITALY, 9-, Novartis, Hyderabad, INDIA, 10Oncology, Dept. OB&GYN and CCC Munich, LMU University Hospital, Munich, GERMANY, 11Medical Oncology, Institut Gustave Roussy, Villejuif, FRANCE, 12Medical Oncology, UTH San Antonio, San Antonio, TX, 13Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 14Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 15Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, AUSTRALIA, 16Stat, Frontier Science Scotland, Kingussie, UNITED KINGDOM, 17Medical Oncology, Department of Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 18Medical Oncology, Istituto Nazionale dei Tumori (INT), Milano, ITALY. DISCLOSURES: Lambertini: Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, Menarini, Nordic Pharma , Roche, Lilly, Novartis, Pfizer, AstraZeneca, Takeda, Ipsen, Sandoz, Libbs, Daiichi Sankyo, Gilead, Menarini, Gilead, Daiichi Sankyo, Roche, Gilead (to the institution). BACKGROUND: The optimal adjuvant endocrine therapy (ET) for patients (pts) with hormone receptor-positive (HR+)/HER2-positive (HER2+) early breast cancer (EBC) remains controversial. The present analysis investigated the efficacy of different types of ET in pts with centrally tested HR+/HER2+ EBC treated with modern chemotherapy (CT) and trastuzumab (T)-based regimens at 10-year follow-up. Patients and methods: ALTTO (BIG 2-06) is an international phase 3 trial in pts with HER2+ EBC randomized to 4 adjuvant anti-HER2 treatments with CT: T alone, lapatinib (L) alone, their sequence (T->L) or their combination (T+L). Pts in the L alone arm, pts with HR-/HER2+ disease and pts with HR+ tumours who did not start adjuvant ET were excluded from the analysis. HER2 and HR status were centrally tested for all pts. Disease-free survival (DFS), time to distant recurrence (TTDR) and overall survival (OS) were compared between pts who received a selective estrogen receptor modulator (SERM) vs. those who received an aromatase inhibitor (AI). To avoid the risk of immortal time bias, pts with HR+/HER2+ di

ASH 2025: Measurable Residual Disease Can Predict Overall Survival in Patients with Acute Myeloid Leukemia An interview with: Jesse Tettero MD PhD, Amsterdam University Medical Center, Department of Hematology, Amsterdam, Netherlands and: Virginia Tech FBRI Cancer Research Center, Fralin Biomedical Research Institute, Washington, USA. Reporting from: American Society of Hematology 2025 Annual Meeting, Orlando, USA ORLANDO, USA—Measurable residual disease (MRD) could soon emerge as a key surrogate endpoint in clinical studies of acute myeloid leukemia indicating overall survival, and speed the introduction of effective new agents. That’s according to findings from the HARMONY Alliance study of European randomized trials reported to the 2025 Annual Meeting of the American Society of Hematology Annual Meeting. After speaking at the conference, the first author Jesse Tettero, from Amsterdam University Medical Center, Department of Hematology in Amsterdam, Netherlands and Virginia Tech FBRI Cancer Research Center, Fralin Biomedical Research Institute, in Washington, USA, discussed the findings with Audio Journal of Oncology correspondent, Peter Goodwin: Audio Journal of Oncology with Jesse Tettero MD PhD IN: [GOODWIN]” I am at the American ….. OUT: …….I’m Peter Goodwin 9:09secs PUBLICATION: “Blood”, 2025: Blood (2025) 146 (Supplement 1): 343. ASH 2025 ABSTRACT Number: 343 LEAD AUTHOR: Jesse Tettero Amsterdam University Medical Center, Department of Hematology, Amsterdam, Netherlands and: Virginia Tech FBRI Cancer Research Center, Fralin Biomedical Research Institute, Washington, United States TITLE: Validation of measurable residual disease as a surrogate endpoint in acute myeloid leukemia: A HARMONY Alliance study of European randomized trials AUTHORS: Jesse Tettero, Sträng Eric, Sylvie Freeman, Richard Dillon, Jacqueline Cloos, Peter Valk, Konstanze Döhner, Michael Heuser, Christoph Röllig, Christian Thiede, Axel Benner, Luciana Carota, Daniele Dall’Olio, Ana Garcia, Alberto Hernandez Sanchez, Sean Johnson, Soren Lehmann, Javier Martinez Elicegui, Rabea Mecklenbrauck, Klaus Metzeler, Marta Sobas, Ian Thomas, Amin Turki, Laura Tur Gimenez, Brain Huntley, Nigel Russell, Jurjen Versluis, Hartmut Döhner, Jesus Maria Hernandez Rivas, Lars Bullinger, Gert J. Ossenkoppele ABSTRACT Introduction: Measurable residual disease (MRD) prior to consolidation therapy is a strong prognostic biomarker for relapse and long-term survival in acute myeloid leukemia (AML). Beyond its prognostic role, MRD is increasingly used to guide therapeutic decisions. A logical next step is regulatory acceptance of MRD as a (co-)primary endpoint in AML, as recently granted by the FDA for MRD in multiple myeloma. However, acceptance in AML is hampered by disease heterogeneity, variability in MRD assessments and a lack of trial-level validation. As MRD-guided treatment becomes more common, future trial outcomes may be confounded by such interventions. Thus, establishing MRD now as a surrogate endpoint is critical to enable accelerated drug approval in AML. Here, we evaluate both individual- and trial-level surrogacy of MRD assessed by multiparameter flow cytometry (MFC) and qPCR for mutant NPM1 using harmonized patient-level data from seven prospective randomized phase II/III trials. METHODS: We included patient-level data from 1,858 adult with AML enrolled in trials conducted by AMLSG, HOVON-SAKK, SAL, and UK-NCRI, collected through the HARMONY Alliance. Eligible trials involved randomization to experimental or placebo treatment added to a standard intensive induction chemotherapy, with ≥20 patients per arm and per MRD subgroup. Patients were included if they had a MRD assessment after two chemotherapy cycles by either MFC or qPCR for mutant NPM1. Data were harmonized using the OMOP common data model. Following FDA guidance, we analyzed two levels of surrogacy. For individual-level surrogacy, we examined the association between MRD status and overall survival (OS) using Plackett’s copula models and multivariable Cox regression. For trial-level surrogacy, we quantified the relationship between treatment effects on MRD and OS using hazard ratios (HR) and odds ratios (OR) in weighted least-squares regression. A coefficient of determination (R²) >0.8 with 95% CI lower bound >0.6 was considered strong trial-level surrogacy, consistent with previously accepted surrogate endpoints. Subgroup analyses were conducted by MRD method and transplant status. RESULTS: The included trials were AMLSG 09-09 (qPCR MRD assessment), three HOVON-SAKK trials (AML-102, AML-103, AML-132; all MFC), the SAL cohort (qPCR), and the UK-NCRI AML17 trial, which included two separate randomizations (both MFC- and qPCR-MRD). In multivariable analysis, MRD positivity was associated with significantly worse OS across the cohort (HR: 1.66, 95% CI: 1.33–2.07, p<0.001). This association persisted when stratified by MRD met

Next Generation Sequencing-Assessed Minimum Residual Disease Identifies Young Patients with High-risk/Relapsed B-cell Acute Lymphoblastic Lymphomas Who Can Omit Pre-Transplant Total Body Irradiation An interview with: Hisham Abdel-Azim MD MS, Chief, Division of Transplant/Cell Therapy and Hematological Malignancies, Cancer Center, Departments of Pediatrics and Medicine, Loma Linda University School of Medicine, Children Hospital and Medical Center, Loma Linda CA, United States ORLANDO, Florida—Total body irradiation before allogeneic hematopoietic cell transplantation can be avoided in patients with B-cell lymphomas if you monitor their initial treatment responses by assessing minimum residual disease using next generation sequencing rather than by traditional flow cytometry. This finding has emerged from the phase two EndRAD trial reported at the 2025 Annual Meeting of the American Society of Hematology by Hisham Abdel-Azim MD MS, Chief, Division of Transplant/Cell Therapy and Hematological Malignancies, Cancer Center, Departments of Pediatrics and Medicine, Loma Linda University School of Medicine, Children Hospital and Medical Center, Loma Linda CA, United States. After his talk at the conference he discussed the findings with the Audio Journal of Oncology’s Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Hisham Abdel-Azim MD MS IN: [GOODWIN]”I’m reporting now from ……. OUT: …for the Audio Journal of Oncology” 11:12 secs PUBLICATION: BLOOD, 2025: https://ashpublications.org/blood/article/146/Supplement%201/163/553049/High-event-free-EFS-and-overall-survival-OS-after TITLE: High event-free (EFS) and overall survival (OS) after non-total body irradiation (TBI) conditioning and allogeneic hematopoietic cell transplantation (HCT) in next-generation-sequencing minimal residual disease (NGS-MRD) negative B-acute lymphoblastic leukemia (B-ALL): Results from the EndRAD trial (PTCTC ONC1701) AUTHORS Hisham Abdel-Azim, Troy Quigg, Neena Kapoor, Yueh-Yun Chi, Christine Higham, Amy Keating, Vanessa Fabrizio, Jodi Skiles, Shalini Shenoy, Sajad Khazal, Aliza Gardenswartz, Lisa Madden, Jordan Milner, Rachel Phelan, Emi Caywood, Ulrich Duffner, Jonathan Fish, Jorge Galvez Silva, Alfred Gillio, Rabi Hanna, Jeffrey Huo, Nahal Lalefar, Kris Mahadeo, Kevin McNerney, J. Gregory Dolan, Dana Salzberg, Heather Stefanski, Michael Pulsipher LEAD INSTITUTION: Division of Transplant/Cell Therapy and Hematological Malignancies, Cancer Center, Departments of Pediatrics and Medicine, Loma Linda University School of Medicine, Children Hospital and Medical Center, Loma Linda, United States ABSTRACT Introduction: HCT is an established curative treatment for children, adolescents, and young adults (CAYA) with high-risk/relapsed B-ALL. Inclusion of TBI in HCT conditioning has been shown to be superior to non-TBI approaches for B-ALL, but is associated with significant late effects. Based upon retrospective data showing low rates of relapse, we hypothesized that patients with negative pre-HCT MRD by next-generation-sequencing of IgH B-cell receptor rearrangements (NGS-MRD) could achieve 2-year EFS exceeding 75% with a non-TBI regimen, an outcome comparable to those receiving TBI-based regimens. METHODS: The Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) conducted a phase II prospective trial at 45 centers in North America (ONC1701 EndRAD: NCT03509961) between 2018 and 2025 to evaluate outcomes of myeloablative non-TBI conditioning regimens for allogeneic HCT in B-ALL patients at lower risk for relapse defined by absence of NGS-MRD (Clonoseq) of B-cell receptor rearrangements (BCR) just prior to HCT. Eligibility criteria included age >/= 1 year to <31 years, first or second complete remission status (CR1/CR2), and no isolated or combined CNS disease at relapse. Prior blinatumomab, inotuzumab ozogamicin, or CAR-T treatments were allowed. All graft sources were permitted. Mismatched related/haploidentical grafts received post-transplant cyclophosphamide or TCRαβ/CD19 depletion according to institutional preference. All patients received myeloablative non-TBI conditioning. Graft-versus-host disease (GVHD) prophylaxis was according to graft source and institutional standards. RESULTS: Fifty-one patients (51% males) in CR1 (49%) or CR2 (51%) status received HCT. Median age (range) at initial diagnosis and HCT were 11.9 (1.2-28.1) and 13.5 (2.3-32.5) years, respectively. Of patients enrolled, 33% were White/Non-Hispanic, 37% Hispanic, 12% Black or African American, and 18% other. Prior to HCT, 28 patients (55%) received blinatumomab, 1 (2%) received inotuzumab, while 11 (21%) received CAR-T, 7 (14%) received 2 prior immunotherapies, and 4 (8%) had no prior immunotherapy. Forty-four patients (86%) received the preferred study non-TBI conditioning regimen (busulfan, fludarabine, thiotepa); 2 comparable allowed regimens were received: fludarabine, melphalan, and thiotepa by 3 patients (6%) and melphalan, fludarabine, clofarabine, an

2025 San Antonio Breast Cancer Symposium: Selective Estrogen Degrader Giredestrant Improves on Standard Endocrine Therapy for Patients with ER-positive, HER2-negative Early Breast Cancer: Phase III lidERA Breast Cancer trial Findings An interview with: Aditya Bardia MD MPH, Professor of Medicine and Director of Translational Research Integration, University of California, Los Angeles and Jonsson Comprehensive Cancer Center, Los Angeles, California USA. SAN ANTONIO, USA—Significant and clinically meaningful improvements in disease-free survival were reported from the Phase III lidERA Breast Cancer trial at the 2025 San Antonio Breast Cancer Symposium, in San Antonio, USA. First author of the study, Aditya Bardia MD MPH, Professor of Medicine and Director of Translational Research Integration at University of California, Los Angeles and the Jonsson Comprehensive Cancer Center, in Los Angeles, California, met up with Audio Journal Oncology reporter, Peter Goodwin. Audio Journal of Oncology with: Aditya Bardia MD MPH IN “[GOODWIN] I am at the San Antonio ……. OUT: …….of Oncology. I’m Peter Goodwin” 7:42 secs San Antonio Breast Cancer Symposium ABSTRACT: GS1-10 “Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial Speaker: Aditya Bardia, University of California Los Angeles, Los Angeles, CA Authors: Bardia1, P. Schmid2, M. Martín3, S. Hurvitz4, K. Jung5, M. Rimawi6, S. Saji7, G. Werutsky8, N. Harbeck9, S. Loi10, A. Ogiya11, M. Ruiz-Borrego12, A. Alacacıoğlu13, J. Wu14, C. Ye15, M. Liste-Hermoso16, N. Withana16, T. Badovinac Crnjevic17, M. Shah18, P. Pérez-Moreno19, C. Geyer, Jr.20; 1University of California Los Angeles, Los Angeles, CA, 2Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UNITED KINGDOM, 3Universidad Complutense, GEICAM, CIBERONC, Madrid, SPAIN, 4Department of Medicine, UW Medicine, Fred Hutchinson Cancer Center, Seattle, WA, 5Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KOREA, REPUBLIC OF, 6Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 7Department of Medical Oncology, Fukushima Medical University, Fukushima, JAPAN, 8Breast Cancer Program, Latin American Cooperative Oncology Group and Centro de Pesquisa em Oncologia, Hospital Sao Lucas PUCRS, Porto Alegre, JAPAN, 9Department of Obstetrics and Gynecology, LMU University Hospital, Munich, GERMANY, 10Division of Cancer Research, Peter MacCallum Cancer Centre and The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, AUSTRALIA, 11Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, JAPAN, 12Breast Cancer Unit, Hospital Universitario Virgen del Rocío, Sevilla, SPAIN, 13Department of Oncology, İzmir Kâtip Çelebi University, Atatürk Training and Research Hospital, İzmir, TURKEY, 14Department of Breast Surgery, Cancer Hospital/Institute, Fudan University, Shanghai, CHINA, 15Department of Oncology Biostatistics, Genentech, Inc., South San Francisco, CA, 16Global Product Development – Clinical Science Oncology (PDOH), F. Hoffmann-La Roche Ltd, Basel, SWITZERLAND, 17PDO – Clinical Science Oncology, F. Hoffmann-La Roche Ltd, Basel, SWITZERLAND, 18Product Development Safety, Genentech, Inc., South San Francisco, CA, 19Product Development Oncology/Hematology (PDOH), Genentech, Inc., South San Francisco, CA, 20Department of Medicine, University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center, Pittsburgh, PA. Background: Adjuvant (adj) endocrine therapy (ET) is the mainstay treatment (tx) for estrogen receptor-positive, HER2-negative early breast cancer (ER+ HER2- eBC). However, up to 1/3 of patients (pts) eventually experience recurrence. Clinically, there is an unmet need for more tolerable and efficacious ET to improve adherence and pt outcomes. Giredestrant, a next-generation oral selective estrogen receptor antagonist and degrader (SERD), was shown to be more potent than other SERDs (Liang 2021; Bardia 2023) and demonstrated superior antiproliferative activity vs anastrozole in the neoadj coopERA BC trial (Hurvitz 2023). Results of the prespecified interim analysis of the global, randomized lidERA BC trial (NCT04961996) are presented. Methods: Pts with Stage I-III ER+ HER2- eBC were randomized 1:1 to giredestrant 30 mg oral daily (with an LHRH agonist in pre- and peri-menopausal women, and men) or standard-of-care ET (tamoxifen or aromatase inhibitor) for 5 years (yr). The primary endpoint was invasive disease-free survival (IDFS). Key secondary endpoints were overall survival (OS), distant recurrence-free interval (DRFI), and safety. Results: 4170 pts were randomized (Aug 2021-Sep 2023): 2084 to giredestrant; 2086 to standard-of-care ET. Median age was 54.0 yr; 59.3% of pts were postmenopausal; 13.0

ASH 2025 Orlando: Childhood Leukemia Cured But Families Broke. “Financial Toxicity” is Often More Worrying than you Child’s Cancer An interview with: Daniel J Zheng MD, MHS, MSHP, Instructor, Children’s Hospital of Philadelphia, Attending Oncologist, Division of Oncology, Philadelphia PA, United States ORLANDO, USA—Although most children with acute lymphoblastic leukemia can look forward to a cure, their families may face catastrophic financial hardship, according to Daniel Zheng, an Instructor and Attending Oncologist at the Division of Oncology, Children’s Hospital of Philadelphia in Philadelphia, PA, United States. After reporting on the challenge families face of “financial toxicity” from extended curative treatment for ALL Dr. Zheng talked about his findings from the Dana Farber Cancer Institute ALL 16-001 Trial with Audio Journal of Oncology correspondent, Peter Goodwin: Audio Journal of Oncology: Daniel Zheng IN: “[GOODWIN] I’m reporting direct … OUT: Oncology, I’m Peter Goodwin 7:38secs American Society of Hematology 2025 Annual Meeting Abstract 710: “Cumulative incidence of household material hardship and income loss as measures of financial toxicity during pediatric acute lymphoblastic leukemia (ALL) treatment: A report from the DFCI: ALL 16-001 Trial” Authors Daniel Zheng1, Eva Robinson 2, Yael Flamand, 3, Rahela Aziz-Bose 4, Victoria Koch3, Peter Cole5, Lisa Gennarini6, Kelly Getz7, Justine Kahn8, Kristine Karvonen9, Colleen Kelly10, Kara Kelly11, Bruno Michon12, Haley Newman1, Morgan Paul13, Thai Tran14, Puja Umaretiya15, Jennifer Welch16, Edie Weller2, 17, Lewis Silverman8, Kira Bona 10 1 Children’s Hospital of Philadelphia, Division of Oncology, Philadelphia, PA, United States, 2 Boston Children’s Hospital, Biostatistics and Research Design Center, Boston, MA, United States, 3 Dana-Farber Cancer Institute, Boston, MA, United States, 4 Dana-Farber Cancer Institute, Department of Pediatric Oncology, MD, MPH, MA, United States, 5 Rutgers Cancer Institute, New Brunswick, NJ, United States, 6 Montefiore Medical Center, Bronx, NY, United States, 7 University of Pennsylvania, Department of Epidemiology, Philadelphia, PA, United States, 8 Columbia University Irving Medical Center, Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, New York, NY, United States, 9 Seattle Children’s Hospital, Division of Pediatric Hematology-Oncology, Seattle, WA, United States, 10 DanaFarber Cancer Institute, Department of Pediatric Oncology, Boston, MA, United States, 11 Roswell Park Comprehensive Cancer Center, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Department of Pediatrics, Buffalo, NY, United States, 12 Centre Hospitalier Universitaire de Quebec, SaintFoy, QC, Canada, 13 Dana-Farber Cancer Institute, Department of Data Science, Boston, MA, United States, 14 Charles-Bruneau Cancer Center, CHU Ste-Justine, University of Montreal, Division of Pediatric Hematology-Oncology, Montreal, QC, Canada, 15 UT Southwestern Medical Center, Department of Pediatrics, Dallas, TX, United States, 16 Hasbro Children’s Hospital/Brown University, Division of Pediatric Hematology Oncology, Providence, RI, United States, 17 Harvard Medical School, Department of Pediatrics, Boston, MA, United States Abstract Body, Introduction: Over 90% of children with acute lymphoblastic leukemia (ALL) will survive their cancer in the context of >2 years of multi-agent chemotherapy. This intensive treatment paradigm may lead to significant treatment-related financial toxicity for families— an outcome highly relevant to long-term child and family well-being. The magnitude and trajectories of financial toxicity are unknown in pediatric oncology, and necessary to inform optimal screening and intervention strategies for children with cancer and their families. Development of new household material hardship ([HMH], housing, food, or utility insecurity) or income loss during cancer treatment are concrete, targetable metrics of financial toxicity. We present results from Dana-Farber Cancer Institute (DFCI) ALL Consortium Trial 16-001, the first pediatric oncology clinical trial to systematically collect longitudinal HMH and household income data as an embedded correlative trial aim. Methods: DFCI 16-001 (NCT03020030) enrolled children ages 1-<22 years withde novo B- or T-cell ALL at 8 US and Canadian centers from 2017-2021. Participants <18 years were eligible to opt-in to the correlative HMH study at time of initial trial consent. Parents/guardians of participants completed surveys within 32-days of trial enrollment and longitudinally at 6-, 12-, and 24-months. Financial toxicity was the primary endpoint of interest for this secondary analysis, defined by two variables: (1) development of any new HMH domain (food, housing, or utility insecurity) at 6-24 months as compared to baseline and (2) catastrophic income loss defined as ≥25% annual household income loss

https://www.audiomedica.com/wp-content/2025/12/251209-0900-Peihua-Lu-Robert-Chiesa-C2998-Discussion-at-ASH-AJO-PRODUCTION-MASTER.mp3Dramatic Remissions with “Off-the-Shelf” and “Base Edited” CAR T-cell Therapies in Children with Relapsed/Refractory T-Cell Malignancies A discussion interview with Peihua Lu MD from Lu Daopei Hospital in Beijing, China and Robert Chiesa MD PhD from Great Ormond Street Hospital for Children, London, UK, at the American Society of Hematology Annual Meeting in Orlando, Florida, USA ORLANDO, USA—Children and young adults whose T-cell malignancies had become refractory to all standard treatments have been rescued by means of two different chimeric antigen receptor T-cell therapies: one developed commercially in China and the other created in the laboratory of a leading children’s hospital in London by means of a new method of engineering DNA called: “base editing”.   At the 2025 American Society of Hematology annual meeting in Orlando, Florida, lead author of the Chinese study, Peihua Lu MD from Lu Daopei Hospital in Beijing and team-leader Robert Chiesa MD PhD from Great Ormond Street Hospital for Children, London, UK, met up with Audio Journal of Oncology anchor, Peter Goodwin, to discuss their pioneering early studies which seem to offer hope for patients and their families.   Audio Journal of Oncology: Peihua Lu MD and Robert Chiesa MD PhD IN: “[GOODWIN] Welcome to…. OUT: ……..from all of us, Good-bye ” 33:51   A discussion on ASH ABSTRACTS at the 2025 Annual Meeting: Abstract 1042: “CTD402, allogeneic anti-CD7 CAR t-cell, in relapsed or refractory (R/R) t-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) – report of clinical outcomes at the recommended phase 2 dose (RP2D)” Abstract 1041: “Universal base-edited CAR7 T cells for T-cell acute lymphoblastic leukemia”    

An interview with Jeanne Tie MD, Medical Oncologist, Peter MacCallum Cancer Centre and Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. BERLIN, Germany—Liquid biopsy as a means of monitoring disease control in patients with stage three colon cancer has been investigated in a study from Melbourne, Australia reported to the 2025 Annual Congress of the European Society for Medical Oncology, ESMO. The aim was to discover whether patients with ctDNA negative biopsy findings could safely avoid chemotherapy and be spared toxicities including neuropathy. After reporting findings from the AGITG DYNAMIC-III trial, lead author Jeanne Tie MD, who is a Medical Oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia, discussed the results with the Audio Journal of Oncology’s reporter, Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY with：Jeanne Tie MD. IN: “[GOODWIN] I am at the European Society for ….. OUT: …..Audio Journal of Oncology, I’m Peter Goodwin. 10:20 sec ESMO 2025 ABSTRACT LBA9 (Presidential Symposium): “ctDNA-guided adjuvant chemotherapy de-escalation in stage III colon cancer: Primary analysis of the ctDNA-negative cohort from the randomized AGITG DYNAMIC-III trial (Intergroup study of AGITG and CCTG)” Speaker: Jeanne Tie (Melbourne, Australia, VIC) Authors: Jeanne Tie (Melbourne, Australia, VIC) Yuxuan Wang (Baltimore, United States of America) Jonathan M. Loree (Vancouver, Canada) Joshua Cohen (Baltimore, United States of America) David Espinoza (Camperdown, Australia) Rachel Wong (Box Hill, Australia) Timothy J. Price (Woodville, Australia) Niall Tebbutt (Heidelberg, Australia) Matthew Burge (Herston, Australia) James Lynam (Waratah, Australia) Belinda Lee (Melbourne, Australia) Samuel J. Harris (Bendigo, Australia) Lorraine Chantrill (Wollongong, Australia) Daniel A. Breadner (London, Canada) Christopher O’Callaghan (Kingston, Canada) Chetan Bettegowda (Baltimore, United States of America) Nicholas Papadopoulos (Baltimore, United States of America) Kenneth Kinzler (Baltimore, United States of America) Bert Vogelstein (Baltimore, United States of America) Peter Gibbs (Parkville, Australia) Background Adjuvant chemotherapy (ACT) benefit is uncertain for any individual patient (pt). Post-surgery circulating tumour DNA (ctDNA) testing could support risk-adjusted treatment selection. The DYNAMIC-III study explored ACT de-escalation or escalation, informed by post-surgery ctDNA results. Methods In this multicentre, randomised, phase II/III trial, pts with stage III colon cancer underwent tumour-informed ctDNA testing 5-6 weeks post-surgery and were randomised (1:1) to ctDNA-guided or standard management. Clinicians pre-specified standard ACT. In the ctDNA-guided arm, ctDNA-negative results prompted ACT de-escalation: from 6 to 3 months of fluoropyrimidine (FP) or observation, from 3 months of doublet to single-agent FP, or from 6 months of doublet to 3 months doublet or single-agent FP. The primary endpoint was 3-year recurrence-free survival (RFS). A sample size of 750 provided 80% power with a one-sided 97.5% CI to demonstrate non-inferiority (NI) with a NI margin of 7.5%. Results Of 968 evaluable pts, 702 (72.5%) were ctDNA-negative; 353 assigned to ctDNA-guided and 349 to standard management. Median follow-up was 45 months. 319 (90.4%) pts received ctDNA-guided per-protocol de-escalation. Treatment de-escalation reduced oxaliplatin-based chemotherapy use versus standard management (34.8% vs 88.6%, P < 0.001) and lowered grade 3+ adverse events of special interest (6.2% vs 10.6%, P = 0.037) and treatment-related hospitalisation (8.5% vs 13.2%, P = 0.048). However, non-inferiority of ctDNA-guided de-escalation was not confirmed (3-year RFS, 85.3% vs 88.1%; difference = -2.8%; 97.5% lower CI = -8.0%). Pre-planned subgroup analysis suggested de-escalation may be non-inferior in clinical low-risk (T1-3N1) tumours (3-year RFS, 91.0% vs. 93.2%; difference = -2.2%; 97.5% lower CI = -7.2%). Conclusions Stage III colon cancer pts with negative post-surgery ctDNA had low recurrence risk. ctDNA-guided de-escalation is feasible, substantially reduces oxaliplatin exposure and adverse events, with outcomes approaching standard management, especially for clinical low-risk tumours. Clinical trial identification ACTRN12617001566325 Date registered: 21 November 2017. Legal entity responsible for the study Australasian GastroIntestinal Trials Group (AGITG). Funding Marcus Foundation, NHMRC, Virginia and Ludwig Fund for Cancer Research, Lustgarten Foundation, Conrad R Hilton Foundation, Sol Goldman Charitable Trust, NIH, Eastern Health Research Foundation (Zouki Research Grant), Canadian Cancer Society, Canadian Institutes of Health Research (CIHR).

Chemo-Free Regimen with Neoadjuvant CDK 4/6 Inhibition plus Endocrine Therapy Benefits Patients with High-Risk ER+ HER2- Early Breast Cancer An interview with: Paul H Cottu MD PhD, Medical Oncologist and Associate Professor, Institute Curie, Paris, France BERLIN, Germany—Patients with high-risk, hormone receptor positive, HER2 negative early breast cancers, who would typically be candidates for chemotherapy, had good clinical responses, high biological responses and good rates of surgery in a clinical trial using a chemotherapy-free neoadjuvant regimen consisting of letrozole hormone therapy plus abemaciclib CDK 4/6 inhibition. Medical Oncologist Paul Cottu MD PhD from the Institute Curie in Paris, France, reported findings from RIBOLARIS trial at the 2025 Annual Congress of the European Society for Medical Oncology held in Berlin. At his poster during the conference he talked about the study findings with Audio Journal of Oncology reporter Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY Paul H Cottu MD PhD IN: “[GOODWIN] I am at the European ….. OUT: …I’m Peter Goodwin 7:56secs ESMO ABTRACT 296O: “Risk of recurrence (ROR) after neoadjuvant ribociclib plus ET in clinically high-risk ER+/HER2− BC: Preliminary analysis of the SOLTI-RIBOLARIS trial” Speaker: Paul H. Cottu (Paris, France) Authors: Paul H. Cottu (Paris, France) Aleix Prat (Barcelona, Spain) Tomás Pascual (Barcelona, Spain) Huilin Hu (East Hanover, United States of America) Estelle Roux (Basel, Switzerland, NJ) Francisco Javier Salvador Bofill (Seville, Spain) Joana M. Ribeiro (Villejuif, France) Isabel Blancas López-Barajas (Granada, Spain) Thomas Bachelot (Lyon, France) Jerome Lemonnier (Paris, France) Juan M. Ferrero-Cafiero (Barcelona, Spain) Pablo Tolosa Ortega (Madrid, Spain, Valencia) Antonio Mulero-Sánchez (Barcelona, Spain) Thayane Antoniolli Crestani (Brussels, Belgium) Roisin M. Connolly (Cork, Ireland, MD) Cynthia X. Ma (St. Louis, United States of America) Antonio C. Wolff (Baltimore, United States of America, MD) Guillermo Villacampa (Barcelona, Spain) Thibault De La Motte Rouge (Rennes, France) Joaquín Gavilá-Gregori (Valencia, Spain) Background The CDK4/6 inhibitors (CDK46/i) are approved for early-stage HR+/HER2− breast cancer (BC). The randomized neoadjuvant NeoPAL and CORALLEEN trials provided proof of concept that CDK4/6i in combination with endocrine therapy (ET) have similar activity to multi-agent chemotherapy in pts with luminal B-PAM50 based- BC subtype. The PAM50-derived ROR score was identified as an endpoint of interest after neoadjuvant CDK4/6i-ET. The RIBOLARIS trial was designed to evaluate whether pts with ROR-low disease following neoadjuvant ribociclib (RIB) and ET can safely omit adjuvant chemotherapy. Methods RIBOLARIS is an open-label, single-arm, multicenter trial in pts with primary operable stage II, grade 2/3, Ki67 ≥20%, HR+/HER2− BC who are candidates for adjuvant chemotherapy. The study evaluates safety and long-term efficacy of a non-chemo regimen (RIB-ET) in pts with tumors showing a ROR-low score after 6 neoadjuvant cycles of RIB-ET (600 mg/day 3 weeks ON/1 week OFF + ET: letrozol 2.5 mg/day) followed by surgery (within 10 days). Pts with ROR-med/high tumors will receive chemotherapy-based treatment followed by RIB-ET. This preplanned Interim Analysis analyzed safety and efficacy after 686 surgeries. We expected at least 40% of the pts to achieve a ROR-low score after neoadjuvant RIB-ET. Results Among the enrolled pts, baseline characteristics included: median age 57 (38-84), postmenopausal status 62%, tumor stage IIA 60%, node-negative 60%, and histological grade 2 74%. At data cut-off, 686 out of 1100 surgeries (62.4%) were performed. Interestingly, we observed that 361 pts (52.6%) achieved a ROR-low score (Mean 11.3, 95% CI 10.5-12.2), while 325 pts (47.4%) had a med/high ROR score (Mean 36.9, 95% CI 34.2-39.5). The most common grade 3-4 severity TEAEs were neutropenia (grade 3: 46.3%; grade 4: 3.5%) and transaminases increased (grade 3: 10.4%; grade 4: 1.5%). Conclusions These preliminary results from the RIBOLARIS trial confirm and extend the findings from CORALLEEN and NeoPAL trials, demonstrating that a subset of pts with early-stage HR+/HER2− BC achieve ROR-low disease after neoadjuvant RIB-ET and may be candidate to spare chemotherapy. There was no new safety signal. Clinical trial identification NCT05296746.

An interview with Li Zhang MD, Medical Oncologist and Full Professor, Sun Yat-sen University Cancer Center, Guangzhou, China BERLIN, Germany—A doubling of progression-free survival, and highly statistically significant benefit for overall survival, has been achieved in patients with epidermal growth factor- (EGFR-) mutated non-small cell lung cancers that had become refractory to EGFR tyrosine kinase inhibitor therapy in a study in which treatment with the antibody drug conjugate (ADC) sacituzumab tirumotecan was compared with standard platinum-based chemotherapy. At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Professor Li Zhang MD, a medical oncologist and full professor at Sun Yat-sen University Cancer Center in Guangzhou, China, reported findings from the randomized, multi-center phase III OptiTROP-Lung04 study at a late-breaking session. After his talk he discussed the findings with Audio Journal of Oncology reporter, Peter Goodwin: AUDIO JOURNAL OF ONCLOGY: Li Zhang MD IN: “[GOODWIN] I’m here at ……OUT: …..I’m Peter Goodwin 8:42 secs ESMO ABSTRACT LBA5: Sacituzumab tirumotecan (sac-TMT) vs platinum-based chemotherapy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) following progression on EGFR-TKIs: results from the randomized, multi-center phase III OptiTROP-Lung04 study Speaker: Li Zhang (Guangzhou, China) Authors: Li Zhang (Guangzhou, China) Wen Feng Fang (Guangzhou, China) Lin Wu (Changsha, China) Xiangjiao Meng (Jinan, China) Yu Yao (Xi’an, Shaanxi Province, China) Wei Zuo (Nanchang, China) Wenxiu Yao (Chengdu, China) Yanyan Xie (Nanning, China) Yu Zhang (Mianyang, China) Jiuwei Cui (Changchun, China) Yongchang Zhang (Changsha, China) Xingya Li (Zhengzhou, China) Wu Zhuang (Fuzhou, China) Jian Fang (Beijing, China) Qiming Wang (Zhengzhou, China) Wei Jiang (Nanning, China) Kai Li (Tianjin, China) Yina Diao (Chengdu, China) Junyou Ge (CHENGDU, China) Yunpeng Yang (Guangzhou, China) Background Sac-TMT is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. Sac-TMT demonstrated significant survival benefits over docetaxel in EGFRm NSCLC after failure of EGFR-TKI and platinum-based chemotherapy (Fang et al., BMJ 2025). Here, we first report the final PFS analysis and preplanned interim OS analysis results from the phase 3 OptiTROP-Lung04 study (NCT05870319). Methods Patients (pts) were randomized (1:1) to receive sac-TMT monotherapy (5 mg/kg Q2W) or chemotherapy (pemetrexed 500 mg/m2 + carboplatin AUC 5 or cisplatin 75 mg/m2 Q3W for 4 cycles followed by maintenance of pemetrexed). The primary endpoint was PFS assessed by blinded independent review committee (BIRC) with OS as a key secondary endpoint tested hierarchically. Results A total of 376 pts (median age 59.5 yrs; 39.6% male; 79.3% ECOG PS 1; 94.7% prior 3rd-generation EGFR TKI) were randomized to the sac-TMT (n=188) or chemotherapy (n=188) groups. At a median follow-up of 18.9 mo, 21.3% of pts (sac-TMT) vs 1.6% (chemotherapy) remained on treatment. Sac-TMT demonstrated highly statistically significant and clinically meaningful improvements in PFS and OS compared to chemotherapy (Table). Grade ≥ 3 TRAEs occurred in 49.5% and 52.2%, and TRSAEs in 7.4% and 17.0% of pts in sac-TMT and chemotherapy arms, respectively. No drug-related interstitial lung disease/pneumonitis occurred in either arm. Sac-TMT (n=188) Chemotherapy (n=188) Median PFS (BIRC), mo (95% CI) 8.3 (6.7 – 9.9) 4.3 (4.2 – 5.5) HR (95% CI) 0.49 (0.39 – 0.62) P-value <0.0001 12-mo PFS rate, %, (95% CI) 32.3 (25.5 – 39.2) 7.9 (4.4 – 12.8) Median OS, mo (95% CI) NR (21.5 – NE) 17.4 (15.7 – 20.4) HR (95% CI) 0.60 (0.44 – 0.82) P-value 0.0006 Adjusted median OS*, mo (95% CI) NR (21.5 – NE) 17.2 (15.4 – 18.9) HR (95% CI) 0.56 (0.41 – 0.77) P-value 0.0002 ORR (BIRC), % (95% CI) 60.6 (53.3, 67.7) 43.1 (35.9, 50.5) Median DOR (BIRC), mo (95% CI) 8.3 (6.2 – 10.0) 4.2 (3.0 – 4.4) Data cutoff: Jul 06, 2025. P-value was presented as one-sided. *censored at the date of initiation of subsequent anti-tumor ADC drug therapy. Conclusions Sac-TMT is the first TROP2 ADC to significantly improve PFS and OS over platinum-based chemotherapy, with manageable safety in EGFR-TKI resistant NSCLC, positioning it as a potential new standard of care for this population. Clinical trial identification NCT05870319. Legal entity responsible for the study Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

An interview with: https://www.audiomedica.com/wp-content/2025/11/251019-Erwei-Song-ESMO-2025-PRODUCTION-MASTER.mp3, Director of Health Science Center, President, Sun Yat-sen Memorial Hospital, Guangzhou (SYSU), Guangzhou, China. BERLIN, Germany—The open-label HORIZON-Breast01 phase-three study has reported early data showing that, for previously treated patients with advanced or metastatic breast cancer, progression-free survival improved from a median of 8.3 months with pyrotinib plus capecitabine standard of care to 30.6 months among patients in the experimental arm who received monotherapy with the new antibody drug conjugate (ADC) trastuzumab resetecan. Furthermore, the ADC had a favorable safety profile with low occurrence of interstitial lung disease (ILD). Findings were reported at the 2025 Annual Congress of the European Society for Medical Oncology by Erwei Song MD PhD, Director of the Health Science Center, President, Sun Yat-sen Memorial Hospital, Guangzhou (SYSU), in Guangzhou, China. After his talk at the conference, Professor Song discussed the findings with Audio Journal of Oncology reporter Peter Goodwin: Audio Journal of Oncology: Erwei Song MD PhD IN: “[GOODWIN] I am at …… OUT: …….of Oncology, I’m Peter Goodwin. 7:42secs ESMO ABSTRACT LBA19: “SHR-A1811 versus pyrotinib plus capecitabine in human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic breast cancer (BC): A multicenter, open-label, randomized, phase III study (HORIZON-Breast01)” Speaker: Erwei Song (Guangzhou, China) Authors: Erwei Song (Guangzhou, China) Herui Yao (Guangzhou, China) Huiping Li (Beijing, China) Yongmei Yin (Nanjing, China) Qing Yuan Zhang (Harbin, China) Shusen Wang (Guangzhou, China) Quchang Ouyang (Changsha, China) Tao Sun (Shenyang, Liaoning, China) Xiaojia Wang (Hangzhou, China) Weimin Xie (Nanning, China) Biyun Wang (Shanghai, China) Wei Li (Changchun, China) Min Yan (Zhengzhou, China) Cuizhi Geng (Shijiazhuang, China) Yuan Peng (Beijing, China) Yaping Yang (Guangzhou, China) Fangli Dong (Shanghai, China) Ying Zhang (Shanghai, China) Lin Cheng (Shanghai, China) Xiaoyu Zhu (Shanghai, China) Background SHR-A1811, a HER2-targeted antibody-drug conjugate, proved substantial single agent antitumor activity in heavily pretreated solid tumors as shown in a global phase 1 trial (J Clin Oncol. 2024). Here, we first report the interim analysis of SHR-A1811 versus pyrotinib plus capecitabine in HER2+ advanced/metastatic BC from the pivotal phase 3 HORIZON-Breast01 study. Methods Taxane- and trastuzumab-pretreated patients (pts) with HER2+ advanced/metastatic BC were randomized (1:1) to receive intravenous SHR-A1811 or oral pyrotinib plus capecitabine. The primary endpoint was PFS by blinded independent central review (BICR). Results As of Jun 30, 2025, 287 pts were randomized (SHR-A1811, n=142; pyrotinib plus capecitabine, n=145; IHC 3+: 76.1% vs. 71.7%; HR+: 47.9% vs. 47.6%; median lines of prior systemic treatments: 1 vs.1; prior pertuzumab: 71.8% vs. 72.4%), with median follow-up of 15.9 months (95% CI 14.6–17.1) for SHR-A1811, and 15.3 months (95% CI 14.3–16.6) for pyrotinib plus capecitabine. The PFS by BICR was significantly improved in the SHR-A1811 group than in the pyrotinib plus capecitabine group (30.6 months vs. 8.3 months; HR 0.22 [95% CI 0.15–0.34]; p<0.0001; table). Although the median OS was not yet reached, SHR-A1811 showed a clear OS benefit trend. Median treatment duration was 19.5 months (95% CI 17.3–NR) with SHR-A1811, 7.1 months (95% CI 5.6–9.2) with pyrotinib, and 7.5 months (95% CI 5.7–9.6) with capecitabine. Similar rates of TRAEs were observed. Interstitial lung disease (ILD) occurred only in 4 pts (2.8%) receiving SHR-A1811 (grade 1/2: 3 [2.1%]; grade 3: 1 [0.7%]). Conclusions SHR-A1811 exhibited significant PFS benefit and strong trend in OS benefit versus pyrotinib plus capecitabine in the second-line therapy in HER2+ advanced/metastatic BC, with favorable safety profile of low ILD occurrence. Clinical trial identification NCT05424835. Legal entity responsible for the study Jiangsu Hengrui Pharmaceuticals Co., Ltd. Funding Jiangsu Hengrui Pharmaceuticals Co., Ltd. Disclosure Dong, Y. Zhang, L. Cheng, X. Zhu: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd.

An interview with: Andrew Clamp MD, PhD, Consultant Medical Oncologist, Christie Hospital, Manchester, UK BERLIN, Germany—An important therapeutic gain in terms of overall- and progression-free survival has been achieved merely by changing the chemotherapy dose schedule given to patients with high-risk stage three or four epithelial ovarian cancer. This was reported from the ICON8B: GCIG phase-three randomised trial by Andrew Clamp MD PhD of the Christie Hospital in Manchester, England, at the 2025 Annual Congress of the European Society for Medical Oncology. Dr. Clamp discussed the findings with our reporter, Peter Goodwin. Audio Journal of Oncology interview: Andrew Clamp MD, PhD IN: “[GOODWIN] I’m at the European ….. OUT: ….Journal of Oncology, I’m Peter Goodwin” 7:21secs https://www.annalsofoncology.org/article/S0923-7534(25)02624-9/pdf ESMO ABSTRACT: 1064O – ICON8B: GCIG phase III randomised trial comparing first-line weekly dose-dense chemotherapy + bevacizumab to three-weekly chemotherapy + bevacizumab in high-risk stage III-IV epithelial ovarian cancer (EOC): Final overall survival (OS) analysis Speaker: Andrew R. Clamp (Manchester, United Kingdom) Authors: Andrew R. Clamp (Manchester, United Kingdom) Iain McNeish (London, United Kingdom) Domenico Radice (London, United Kingdom) Rosemary Lord (Liverpool, United Kingdom) Agnieszka Michael (Guildford, United Kingdom, Surrey) Audrey Cook (Cheltenham, United Kingdom) Roshan Agarwal (Northampton, United Kingdom, Northamptonshire) Axel Walther (Bristol, United Kingdom) Sarah P. Blagden (Oxford, United Kingdom) Dearbhaile O’Donnell (Dublin, Ireland) James D. Brenton (Cambridge, United Kingdom) Sudha Sundar (Birmingham, United Kingdom) Cristiana Sessa (Bellinzona, Switzerland) Laura R. Murphy (London, United Kingdom) Francesca Schiavone (London, United Kingdom) Aleksandra Gentry-Maharaj (London, United Kingdom) Richard S. Kaplan (London, United Kingdom) Mahesh K. Parmar (London, United Kingdom, London) Jonathan A. Ledermann (London, United Kingdom) ESMO Abstract Background In ICON8B the use of dose-dense weekly paclitaxel (ddwT) with 3-weekly (q3w) carboplatin (C) and bevacizumab (BEV) as first-line treatment improved median progression-free survival (PFS) by 5.5 months (m) compared to standard q3w paclitaxel (T) dosing with C+BEV (22.2m vs 16.7m; Hazard Ratio (HR) 0.75, 95% CI 0.62-0.90 p=0.002). We now report the final OS analysis conducted at trial closure. Methods Eligible participants (pts) with high-risk stage III (residual disease >1cm diameter after immediate primary surgery (IPS) or requirement for primary chemotherapy) or stage IV EOC were randomised 1:1:1 to Arm B1 (standard- q3w C AUC5/6+q3w T 175mg/m2+ q3w BEV 7.5mg/kg); Arm B2- (q3w C AUC5/6+ddwT 80mg/m2); Arm B3- (q3w C AUC5/6+ddwT 80mg/m2+ q3w BEV 7.5mg/kg). Up to six cycles chemotherapy and 18 BEV cycles were administered. Arm B2 recruitment discontinued after ICON8 saw no evidence of PFS improvement with q3wCddwT vs q3wCT. OS was a key secondary outcome and pts were followed for survival endpoints until trial closure on 18th Dec 2024 at end of academic funding. Results From 07/2015 to 03/2020 579 pts were randomised to arms B1 + B3. Median age was 64 years; 91% had High Grade Serous Carcinoma; 93% Stage IIIc/IV; 84% primary chemotherapy with planned delayed primary surgery, 14% IPS, 2% inoperable; 50.2% cases sequenced for germline BRCA1/2 mutations. After a median follow-up of 72.0m, 411 deaths were reported (197 in B3; 214 in B1). Median OS was 49.8m (95% CI 43·7-54.5m) in B3 and 39.6m (95% CI 34·7-45·0m) in B1 (HR 0·79, 95% CI 0·65-0·95, p=0·010). In pts receiving primary chemotherapy, median OS was 47.3m (95% CI 42.0-52.6m) in B3 and 37.1m (95% CI 32.3-42.1m) in B1. Conclusions In pts with high-risk stage III-IV EOC, the use of ddwT in combination with q3w C + BEV as first-line systemic therapy improves median OS by 10.2m compared to q3w T dosing. ddwT with q3wC+BEV should now be considered a standard-of-care first-line treatment option in this group. Further research is required to determine whether efficacy of this regimen is impacted by tumour homologous recombination deficiency and intrinsic chemosensitivity. Clinical trial identification ISRCTN10356387. Legal entity responsible for the study University College London. Funding Cancer Research UK and Medical Research Council.

An interview with Nima Nabavizadeh MD, Associate Professor of Radiation Medicine, Oregon Health & Science University (OHSU), Portland, USA, Chief Medical Officer, Cancer Early Detection Research Center, Portland, Oregon.https://www.audiomedica.com/wp-content/2025/11/251107-Nima-Nabavizadeh-MD-ESMO-2024-PRODUCTION-MASTER.mp3 BERLIN, Germany—A pan-cancer early detection test, that identifies “methylation fingerprints” for a wide range of cancers, has been shown to find more cancers sooner than conventional screening according to research reported to the European Society for Medical Oncology (ESMO) 2025 Annual Congress. Nima Nabavizadeh MD, Associate Professor of Radiation Medicine at the Oregon Health & Science University (OHSU) in Portland, USA, who is also Chief Medical Officer of the Cancer Early Detection Research Center in Portland, Oregon gave a report on the safety and performance of the test at the ESMO congress. Afterwards he spoke with our reporter, Peter Goodwin: Audio Journal of Oncology: Nima Nabavizadeh MD IN: “[GOODWIN]I am at the ESMO meeting …. OUT: ……of oncology. I’m Peter Goodwin” 9:55sec ESMO ABSTRACT LBA64: Safety and performance of a multi-cancer early detection (MCED) test in an intended-use population: Initial results from the registrational PATHFINDER II study https://assets.grail.com/wp-content/uploads/2025/10/ESMO-2025_PF2-Initial-Results_Presentation_FINAL-CLEAN-10.16.2025.pdf Speaker: Nima Nabavizadeh (Portland, United States of America) Authors: Nima Nabavizadeh (Portland, United States of America) Charles McDonnell III (Sacramento, United States of America) Dax Kurbegov (Nashville, United States of America) Marc Matrana (New Orleans, United States of America) Shirish Gadgeel (Detroit, United States of America) Raymond H. Kim (Toronto, Canada) Gretchen Stipec (Fountain Valley, United States of America) Kevin Oeffinger (Durham, United States of America) Michael J. Demeure (Newport Beach, United States of America) Roland Matthews (Atlanta, United States of America) Rebecca Kaltman (Fairfax, United States of America) Tamar Toronjadze (Flushing, United States of America) Cora N. Sternberg (New York, United States of America) Jennifer Tran (Washington, United States of America) Natalia Colocci (Mountain View, United States of America) Leonardo Forero (Amarillo, United States of America) Margarita Lopatin (Menlo Park, United States of America) Margaret McCusker (Menlo Park, United States of America) Karthik Giridhar (Rochester, United States of America) Background The MCED test (Galleri®) detects cancer signals from cell-free DNA in blood and predicts cancer signal origin (CSO) to guide diagnostic (dx) evaluation. PATHFINDER 2 (PF2; NCT05155605) assesses its safety and performance in a large, diverse intended-use population. Methods PF2 is a prospective, multicenter, interventional study that enrolled participants (ppts) aged ≥50y with no clinical suspicion of cancer and no cancer diagnosis/treatment in the past 3y. Primary objectives were safety and performance of the MCED test. Ppts with an MCED cancer signal detected (positive) result underwent dx evaluation based on predicted CSO(s). This prespecified initial analysis included ppts with 12m follow-up (fu) as of Dec 31, 2024. A 3y fu is planned. Results 35,878 ppts were enrolled. Of 23,161 performance analyzable ppts with 12m fu, 216 (0.93%) had a positive MCED test. Specificity was 99.6% (95% CI 99.5-99.7%); positive predictive value (PPV) was 61.6% (54.9-67.8%). First CSO prediction accuracy was 91.7% (85.8-95.3%). Episode sensitivity during 12m fu was 73.7% (65.6-80.4%) in a prespecified subgroup of 12 cancers responsible for ⅔ of US cancer deaths and 40.4% (35.3-45.8%) in all cancers. Of 329 ppts with cancer, 200 had screen-detected cancers: 133 by MCED testing (114 new primaries; 19 recurrent), 20 by USPSTF A/B and 47 by USPSTF C recommended screening tests. Of 133 MCED-detected cancers (MCED cancer detection rate: 0.57%), 75.2% do not have common screening options. Of 114 MCED-detected new primaries, 53.5% were stage I-II; 69.3% were stage I-III. Median time to dx resolution was 46d (IQR 42-59). Of 25,114 safety analyzable ppts, 159 (0.6%) had a protocol-directed invasive procedure. Invasive procedures were ∼2x more common for ppts dx with cancer vs not dx after a positive MCED test. Conclusions MCED testing increased the number of screen-detected cancers nearly 7-fold when added to USPSTF A/B recommended screening (3-fold when added to USPSTF A/B/C). Most MCED-detected new primaries were early stage. With PPV exceeding that of standard of care screening tests and a favorable safety profile, these initial PF2 results support the MCED test’s use for population-scale screening. Clinical trial identification NCT05155605. Editorial acknowledgement Medical writing support for the development of this abstract, under the direction of the authors, was provided by Jennifer Hepker, PhD, and Alexandra L. Thomas, PhD, of Cit

An interview with: Xiuning Le MD PhD, Medical Oncologist, Department of Thoracic Medicine, UT MD Anderson Cancer Center, Houston TX BERLIN, Germany—Mutations in the HER2 molecule can be found in a few per cent of non-small cell lung cancers, and these can now be targeted by the new drug sevabertinib that can bring benefit to patients who have the mutation. That’s according to findings from the SOHO-01 study reported at the 2025 Annual Congress of the European Society of Clinical Oncology. After her talk at the congress, first author Xiuning Le MD PhD, who is a medical oncologist in the Department of Thoracic Medicine, at the University of Texas MD Anderson Cancer Center, in Houston, talked about the new data with Audio Journal of Oncology reporter Peter Goodwin: Audio Journal of Oncology; Xiuning Le MD PhD IN: “[GOODWIN] I am at the European Society for Medical ….OUT: ……. For the Audio Journal of Oncology, I’m Peter Goodwin” 10: 18secs 2025 ESMO Berlin ABSTRACT LBA75: Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): Results from the SOHO-01 study Speaker: Xiuning Le (Houston, United States of America) Authors: Xiuning Le (Houston, United States of America) Tae Min Kim (Seoul, Republic of Korea) Xiaorong Dong (Wuhan, China) Herbert Ho Fung Loong (Hong Kong, Hong Kong SAR, China) Nicolas Girard (Paris, France) Shun Lu (Shanghai, China) Hye Ryun Kim (Seoul, Republic of Korea) Boon-Cher Goh (Singapore, Singapore) Arsela Prelaj (Milan, Italy) Yong Fang (Hangzhou, China) Lin Wu (Changsha, China) Yuki Shinno (Tokyo, Japan) Gennaro Daniele (Rome, Italy) Tsung-Ying Yang (Taichung City, Taiwan) Gerrina Ruiter (Amsterdam, Netherlands) Jun Zhao (Beijing, China) Jan Christoph Brase (Basel, Switzerland) Rui Li (Whippany, United States of America) Paolo Grassi (Milan, Italy) Lin Li (Beijing, China) Background Sevabertinib is a potent, reversible, oral HER2 tyrosine kinase inhibitor with FDA Breakthrough Therapy Designation and Priority Review for pretreated patients (pts) with advanced HER2-mutant NSCLC. We report updated efficacy and safety in pretreated and treatment-naïve pts with HER2-mutant NSCLC in the open-label, multicenter Phase I/II SOHO-01 study. Methods Pts with HER2-mutant NSCLC were treated with sevabertinib 20 mg twice daily in 3 cohorts: Cohort D, previous systemic therapy but naïve to HER2 ex20ins-targeted therapy; Cohort E, previous HER2-targeted antibody-drug conjugates; Cohort F, naïve to systemic anti-cancer therapy for advanced disease. The primary endpoint was objective response rate (ORR) by RECIST v1.1 and blinded independent central review. Secondary endpoints were duration of response (DoR) and progression-free survival (PFS). Results At the data cut-off (June 27, 2025), 209 pts with HER2-mutant NSCLC were treated: 81 (D), 55 (E), and 73 (F). ORR (95% CI) was 64% (53, 75; D), 38% (25, 52; E), and 71% (59, 81; F). Median (95% CI) DoR was 9.2 (6.3, 13.5; D), 8.5 (5.6, 16.4; E), and 11.0 (8.1, not evaluable; F) months; 12-month DoR rates (95% CI) were 42% (27, 57; D) and 29% (5, 53; E). Median PFS (95% CI) was 8.3 (6.9, 12.3; D) and 5.5 (4.3, 8.3; E) months, and not reached (F). In Cohort D, pts with baseline brain metastases had a similar ORR to those without (61% vs 65%). Among pts with HER2 tyrosine kinase domain (TKD) mutations, those with Y772_A775dupYVMA had a higher ORR (78% vs 57%) and median PFS (12.2 vs 7.0 months) than those with other HER2 TKD mutations. Overall, grade ≥3 treatment-related adverse events (TRAEs) were reported in 31% of pts. Diarrhea was the most commonly reported TRAE, mostly grade 1/2 (grade 3: 14%). TRAEs led to treatment discontinuation in 3% of pts; none due to diarrhea. There were no reports of interstitial lung disease or pneumonitis. Conclusions Sevabertinib showed rapid and durable responses with a manageable safety profile in pretreated and treatment-naïve pts with advanced HER2-mutant NSCLC. These data support sevabertinib as a potential practice-changing, new targeted therapy for pts with HER2-mutant NSCLC. Clinical trial identification: NCT05099172, March 28, 2025. Editorial acknowledgement: Alice Xue, MSc, Erica Sedgwick, MSc, and Rachel Fairbanks, BA, of Caudex, IPG Health Medical Communications, provided medical writing and editorial assistance in the development of this abstract, funded by Bayer AG. Legal entity responsible for the study: Bayer AG. New England Journal of Medicine https://www.nejm.org/doi/full/10.1056/NEJMoa2511065    

An interview with: Christof Vulsteke MD PhD, Medical Oncologist, Head of the Integrated Cancer Center Ghent, Belgium BERLIN, Germany—Patients with muscle invasive bladder who were ineligible for cisplatin chemotherapy gained large, clinically meaningful and statistically significant benefits from treatment with the antibody drug conjugate enfortumab vedotin combined with pembrolizumab checkpoint inhibition in the phase three KEYNOTE-905 study. At the 2025 Annual Congress of the European Society for Medical Oncology (ESMO) Medical Oncologist Christof Vulsteke, Head of the Integrated Cancer Centre in Ghent, Belgium, reported marked improvements of event-free and overall survival among patients treated with the new combination, in comparison with those receiving standard radical cystectomy plus pelvic lymph node dissection. After his talk in Berlin he gave more details to Audio Journal of Oncology reporter Peter Goodwin: Audio Journal of Oncology: Christof Vulsteke MD PhD; IN: “[GOODWIN] I am at the ESMO meeting in Berlin ……OUT: …Goodwin for the Audio Journal of Oncology, Goodbye 7:12 secs ESMO 2025 ABSTRACT No. LBA2 “Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study” Speaker: Christof Vulsteke (Gent, Belgium) Authors: Christof Vulsteke (Gent, Belgium) Hristos Kaimakliotis (Indianapolis, United States of America) Pongwut Danchaivijitr (Bangkok, Thailand) Maksym Y. Sabadash (Lviv, Ukraine) Alejo Rodriguez-Vida (Barcelona, Spain) Zhentao Zhang (Fort Wayne, United States of America) Vagiz Atduev (Nizhny Novgorod, Russian Federation) Yunus Emre Goger (Konya, Türkiye) Steffen Rausch (Tuebingen, Germany) Seok Ho Kang (Seoul, Republic of Korea) Yohann Loriot (Villejuif, France) Jens Bedke (Stuttgart, Germany) Matthew D. Galsky (New York, United States of America) Peter H. O’Donnell (Chicago, United States of America) Michael Mihm (Chicago, United States of America) Changting Meng (Groton, United States of America) David Huang (Rahway, United States of America) Chethan Ramamurthy (North Wales, United States of America) Blanca Homet Moreno (Madrid, Spain) Anders Ullén (Stockholm, Sweden) Background Radical cystectomy + pelvic lymph node dissection (RC + PLND) is the standard treatment for pts with MIBC who are cisplatin-ineligible. Periop therapy may improve outcomes in these pts. Methods The phase 3 KEYNOTE-905/EV-303 study (NCT03924895) evaluated efficacy and safety of periop EV + pembro and RC + PLND vs RC + PLND in adult pts with MIBC (T2-T4aN0M0 or T1-T4aN1M0) who were cisplatin-ineligible or declined cisplatin. Pts were randomized 1:1 to EV + pembro (3 cycles EV 1.25 mg/kg on d1 and d8 + pembro 200 mg on d1 Q3W, followed by RC + PLND, then 6 cycles EV + 14 cycles pembro) vs control (RC + PLND only). Study therapy continued until progression, unacceptable adverse events (AEs), withdrawal of consent, or completion of planned treatment. The primary endpoint was event-free survival (EFS) by blinded independent central review. Secondary endpoints were overall survival (OS; key), pathological complete response (pCR) rate (key), and safety. Results 170 pts were randomized to EV + pembro and 174 pts to control. >80% of pts were cisplatin-ineligible per Galsky criteria. As of Jun 6, 2025, median follow-up time was 25.6 mo (range, 11.8–53.7). 149 pts (87.6%) in the EV + pembro arm and 156 (89.7%) in the control underwent surgery. EV + pembro significantly improved EFS (median not reached [NR] vs 15.7 mo; HR 0.40; 95% CI 0.28–0.57; P<.001), OS (NR vs 41.7 mo; HR 0.50; 95% CI 0.33–0.74; P<.001), and pCR rate (57.1% vs 8.6%; estimated difference 48.3%; 95% CI 39.5–56.5; P<.001) vs control. Treatment-emergent AEs occurred in 100% (gr ≥3, 71.3%) of pts in the EV + pembro arm and 64.8% (gr ≥3, 45.9%) in the control. Most frequent gr ≥3 AE of special interest (based on distinct prespecified lists for each drug) was severe skin reactions (grouped term; 11.4%) for pembro, and skin reactions (grouped term; 10.8%) for EV. Conclusions Adding periop EV + pembro to surgery significantly and meaningfully improved EFS, OS, and pCR rate in pts with MIBC who were predominantly cisplatin-ineligible. The safety profile of EV + pembro was manageable and consistent with prior reports. This is the first perioperakthrough regimen to improve outcomes vs RC + PLND in this setting and may be a new standard of care. Clinical trial identification: NCT03924895.

An interview with: Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China BERLIN, Germany—In a head-to-head comparison of two antibody drug conjugates used to treat unresectable or metastatic breast cancer, patients treated with trastuzumab botidotin lived more than twice as long before disease progression than those in the control arm receiving trastuzumab emtansine (T-DM1). This finding was announced by Chinese researchers at the 2025 Annual Congress of the European Society of Medical Oncology. Lead author Xichun Hu MD PhD, Professor, Director, Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China talked about the findings of his groups phase three randomized controlled study with Audio Journal of Oncology reporter Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Xichun Hu MD PhD IN: “[GOODWIN] Peter Goodwin at ESMO ..OUT: ..of Oncology, I’m Peter Goodwin 8:30 sec ESMO ABSTRACT LBA24 “Trastuzumab botidotin vs trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic breast cancer: Results from a randomized phase III study” Speaker: Xichun Hu (Shanghai, China) Authors: Xichun Hu (Shanghai, China) Jian Zhang (Shanghai, China) Quchang Ouyang (Changsha, China) Qingyuan Zhang (Harbin, China) Huihui Li (Jinan, China) Xu Wang (Tianjin, China) Ying Wang (Guangzhou, China) Yongmei Yin (Nanjing, China) Shusen Wang (Guangzhou, China) Yuanting Gu (Zhengzhou, Algeria) Tao Sun (Shenyang, China) Jingfen Wang (Linyi, China) Xinhong Wu (Wuhan, China) Fanfan Li (Hefei, China) Xi Chen (Fuzhou, China) Man Li (Dalian, China) Jin Yang (Xi’an, Shaanxi Province, China) Hua Yang (Baoding, China) Xiaoping Jin (Chengdu, China) Junyou Ge (CHENGDU, China) Lecture Time ASTRACT Background Trastuzumab botidotin (A166) is a HER2-directed ADC developed using a stable, protease-cleavable valine-citrulline linker conjugated to the anti-microtubule agent Duo-5. In a phase 1 study, A166 showed promising activity in heavily pretreated patients (pts) with HER2+ breast cancer (BC). Here, we first report the results from a phase 3 study (NCT06968585).   Methods Pts with HER2+ unresectable or metastatic BC who had received at least one prior anti-HER2 therapy were randomized (1:1) to receive A166 (4.8 mg/kg Q3W) or T-DM1 (3.6 mg/kg Q3W) until disease progression or unacceptable toxicity. The primary endpoint was PFS by BICR per RECIST v1.1.   Results A total of 365 pts were randomized (median age 55 years; 73.4% with visceral metastases; 53.4% received ≥2 prior anti-HER2 therapies; 55.9% had prior pyrotinib). As of 26 April 2025, median follow-up was 14.9 mo. Median PFS was significantly longer in A166 than in T-DM1 (11.1 mo vs 4.4 mo; HR 0.39 [95% CI 0.30-0.51], p<0.0001). PFS benefit with A166 was consistently observed regardless of prior lines of anti-HER2 therapy (HR 0.36 for 1 prior line; HR 0.39 for ≥2 prior lines). ORR by BICR was 76.9% vs 53.0%, and mDOR was 12.2 mo vs 5.7 mo. Although OS data were immature, a trend toward benefit was observed in A166 (HR 0.62; 95% CI, 0.38-1.03). Grade ≥3 TEAEs occurred in 69.8% of pts in A166 and 63.7% in T-DM1. The most common grade ≥3 TEAEs (≥5%) were corneal disorder, dry eye, and vision blurred in A166, and platelet count decreased, neutrophil count decreased, hypokalemia, and GGT increased in T-DM1. Among A166-treated pts who experienced any-grade ocular AEs, instrumental activities of daily living (ADL) limitations occurred in 37 (20.3%) pts, and self-care ADL limitations in 13 (7.1%) pts; these resolved in 32 (86.5%) and 12 (92.3%) pts, respectively. TEAEs led to discontinuation in 1.1% of pts in A166 and 3.8% in T-DM1. No TEAE led to death in A166, compared with 1.1% in T-DM1. Conclusions A166 demonstrated statistically significant and clinically meaningful improvement in PFS compared with T-DM1, with a manageable safety profile in pts with HER2+ unresectable or metastatic BC. These results position A166 as a potential new therapeutic option for HER2+ disease. Clinical trial identification NCT06968585. Legal entity responsible for the study Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Funding Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Disclosure Jin, J. Ge: Financial Interests, Institutional, Full or part-time Employment: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. All other authors have declared no conflicts of interest. Xichun Hu MD, PhD Medical Oncology Xuhui, Shanghai, China Xi-Chun Hu, M.D., Ph. D., is currently a Professor, Director of the Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China. Dr. Hu has published more than 170 papers in the journals, such as Lancet Oncology, JCO, and International Journal Cancer, and 5 book chapters. He is vice editor of the ABC (Advanced breast cancer) guideline (Chinese version) and one of the leading authors of the CBCS (Chinese Breast Cancer Society) guideline for

An interview with: Martin Wermke MD, TU Dresden, NCT/UCC Early Clinical Trial Unit and Medical Clinic, Poliklinik I, Natural Centre for Tumor Diseases, Dresden, Germany BERLIN, Germany—The prospect of markedly better outcomes for patients with small cell lung cancer, with “encouraging initial survival outcomes”, was raised by findings from the DeLLphi-303 study, reported at the European Society for Medical Oncology (ESMO) 2025 Annual Congress. The bi-specific T-cell engager drug tarlatamab was included with initial therapy for patients with extensive stage small cell lung cancer. Martin Wermke MD, from TU Dresden, Director of the NCT/UCC Early Clinical Trial Unit and of the Medical Clinic, Poliklinik I, Natural Centre for Tumor Diseases in Dresden, Germany reported the latest study data to the ESMO congress. After his talk he gave the details to our reporter Peter Goodwin: Audio Journal of Oncology; Martin Wermke MD: ”[GOODWIN] Peter Goodwin here at the ESMO meeting ………….of Oncology, I’m Peter Goodwin.” 6:16secs https://pubmed.ncbi.nlm.nih.gov/40934933/ ESMO ABSTRACT 2757O Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study Speaker: Martin Wermke (Dresden, Germany) Authors Martin Wermke (Dresden, Germany) Sally Lau (Toronto, Canada) Mor T. Moskovitz (Petah Tikva, Israel) Ingel Demedts (Roeselare, Belgium) Kelly Paulson (Seattle, United States of America) Aurélie Swalduz (Lyon, France) Cornelius Waller (Freiburg, Germany) Luis Paz-Ares (Madrid, Spain) Makoto Nishio (Koto-ku, Japan) Michael Boyer (Camperdown, Australia, NSW) James Chih-Hsin Yang (Taipei City, Taiwan) Amanda Parkes (Thousand Oaks, United States of America) Yuyang Zhang (Thousand Oaks, United States of America) Ali Hamidi (Thousand Oaks, United States of America) Mukul Minocha (Thousand Oaks, United States of America) Pedro F. Simoes da Rocha (Barcelona, Spain) Background: Tarlatamab with anti-PD-L1 achieved notable survival outcomes with manageable safety as maintenance therapy following 1L platinum-etoposide chemotherapy and anti-PD-L1 (1L chemo-IO) for ES-SCLC. In this phase Ib study (parts 2, 4, 7), the safety and efficacy of adding tarlatamab to 1L chemo-IO was assessed. Methods: Patients (pts) had received 1 cycle of 1L chemo-IO prior to enrollment. On study, pts received 3 cycles of tarlatamab + 1L chemo-IO followed by tarlatamab + anti-PD-L1 Q3W until progression. Tarlatamab was administered 20 mg Q3W with a 1 mg step dose. Primary endpoints included dose-limiting toxicities (DLTs), treatment-emergent (TE), and treatment-related (TR) adverse events (AEs). Key secondary endpoints were objective response (OR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of 96 pts enrolled, 3 (3%) had DLTs. TEAEs and TRAEs were reported in all pts. The most common TRAEs were cytokine release syndrome (CRS, 56%), anemia (54%), and dysgeusia (46%). Grade (Gr) ≥ 3 TRAEs occurred in 72 pts (75%), most commonly neutropenia/neutrophil count decreased (44%), anemia (23%), and lymphopenia/lymphocyte count decreased (11%), primarily within the first two cycles. CRS (54% Gr 1-2; 2% Gr 3-4) and ICANS and associated neurological events (5% Gr 1-2; 1% Gr 3) TRAEs were mostly low grade. Other immune-related AEs were rare (2%). From a baseline scan after 1 cycle of 1L chemo-IO, OR rate following tarlatamab addition to 1L chemo-IO was 71%, with median DOR of 11.0 months (mo) (95% CI 6.7-not estimable). Median PFS was 9.0 mo. With a median follow-up time of 11.3 mo, the Kaplan-Meier estimate of OS at 12 mo was 81% (Table). Results from further follow-up will be presented. Table: 2757O Safety and efficacy of tarlatamab + chemoimmunotherapy as 1L treatment for ES-SCLC Conclusions: The combination of tarlatamab with chemo-IO for 1L treatment of ES-SCLC demonstrated manageable safety with encouraging initial survival outcomes, supporting further investigation of this combination in the phase III DeLLphi-312 study. Clinical trial identification: NCT05361395. Editorial acknowledgement Medical writing support for the development of this abstract was provided by Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and Liz Leight, PhD, an employee of Amgen Inc., and was funded by Amgen Inc. Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc.

An interview with: John P. Crown MD MBA, Consultant Medical Oncologist, St. Vincent’s University Hospital, Dublin, Professor of Translational Cancer Research, Dublin City University, Professor of Medicine, University College Dublin Ireland. BERLIN, Germany—Patients with high-risk node-negative ER-positive HER2-negative early breast cancer who had the CDK 4/6 inhibitor drug ribociclib added to their non-steroidal aromatase inhibitor (AI) adjuvant therapy after surgery had significantly longer freedom from progression to invasive disease compared with patients receiving the AI alone. This is according to five-year data from the NATALEE trial reported at the 2025 Annual Congress of the European Society for Medical Oncology. Professor John P. Crown MD MBA, Consultant Medical Oncologist, from St. Vincent’s University Hospital in Dublin gave reporter Peter Goodwin the latest details: Audio Journal of Oncology, John P. Crown MD MBA, IN: “[GOODWIN] I am at the ESMO meeting, 2025, in Berlin ….OUT: signing off for the Audio Journal of Oncology.” 11:24 secs 2025 ESMO: Proffered Paper Friday 14:00 Oct 17, 2025 Abstract Title: LBA14 – Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): NATALEE 5-year outcomes Speaker: John P. Crown (Dublin, Ireland) Authors: John P. Crown (Dublin, Ireland) Daniil Stroyakovskiy (Moscow, Russian Federation) Denise Yardley (Chattanooga, United States of America) Chiun-Sheng Huang (Taipei City, Taiwan) Peter A. Fasching (Erlangen, Germany) Aditya Bardia (Los Angeles, United States of America) Stephen Chia (Vancouver, Canada) Seock-Ah Im (Seoul, Republic of Korea) Miguel Martin (Madrid, Spain) Binghe Xu (Beijing, China) Carlos H. Barrios (Porto Alegre, Brazil) Michael Untch (Berlin, Germany) Rebecca Moroose (Lake Mary, United States of America) Sara A. Hurvitz (Seattle, United States of America, CA) Gabriel N. Hortobagyi (Houston, United States of America) Dennis Slamon (Los Angeles, United States of America) Frances Visco (Washington, United States of America) Gonzalo Spera (Montevideo, Uruguay) Zheng Li (East Hanover, United States of America) Sherene Loi (Melbourne, Australia, VIC) Background: The phase 3 NATALEE trial demonstrated that adjuvant RIB + NSAI led to a statistically significant invasive disease–free survival (iDFS) benefit in pts with stage II and III HR+/HER2− EBC. We present a protocol-specified 5-year efficacy analysis. Methods: Pts with HR+/HER2− EBC were randomized 1:1 to RIB (400 mg/d; 3 weeks on/1 week off for 3 y) + NSAI (letrozole 2.5 mg/d or anastrozole 1 mg/d for 5 y) or NSAI alone. Men and premenopausal women received goserelin. Pts were included if they had anatomical stage IIA (if N1 [1-3 axillary lymph nodes] or N0 with additional high-risk factors), stage IIB, or stage III disease per AJCC, 8th ed. The primary end point of iDFS and secondary efficacy end points of distant disease–free survival (DDFS), distant relapse–free survival (DRFS), and overall survival (OS) were evaluated using Kaplan-Meier methods. Statistical comparisons were made by stratified log-rank test. Results: At data cutoff (May 28, 2025), all pts were off RIB treatment, and a similar proportion had completed 5 years of NSAI treatment in both arms (RIB + NSAI, 36.5%; NSAI alone, 34.4%). With a median iDFS follow-up of 55.4 months, RIB + NSAI demonstrated persistent iDFS benefit over NSAI alone (hazard ratio [HR], 0.716; 95% CI: 0.618-0.829; nominal 1-sided P<.0001). Absolute iDFS rates were 90.8% vs 88.0% at 3 y, 88.3% vs 83.9% at 4 y, and 85.5% vs 81.0% at 5 y (absolute improvement of 2.7%, 4.4%, and 4.5%, respectively). iDFS benefit was observed across subgroups, including N0 (HR, 0.606; 95% CI: 0.372-0.986). RIB + NSAI also demonstrated continued DDFS (HR, 0.709; 95% CI: 0.608-0.827) and DRFS (HR, 0.699; 95% CI: 0.594-0.824) benefit vs NSAI alone. A positive trend for OS favoring RIB + NSAI (HR, 0.800; 95% CI: 0.637-1.003; nominal 1-sided P=.026) continues to emerge. No new safety signals were observed with a median follow-up time of approximately 2 years after RIB completion. Conclusions: In this 5-year landmark analysis with mature efficacy data, RIB + NSAI reduced the risk of invasive and distant disease recurrence compared with NSAI alone, including in pts with high-risk N0 disease. A positive trend for OS in favor of RIB + NSAI continues to emerge.

An interview with: Javier C Cortés MD PhD, Breast Cancer Medical Oncologist, IOB Madrid, Institute of Oncology, Madrid, and International Breast Cancer Centre, Barcelona, Spain BERLIN, Germany—Treatment with the antibody drug conjugate (ADC) sacituzumab govitecan (that targets the Trop-2 cancer-associated protein, delivering a cytotoxic topoisomerase inhibitor payload) has significantly improved progression-free survival in patients with newly-diagnosed metastatic triple-negative breast cancer who were not candidates for treatment with immune checkpoint inhibition and had received no prior therapy. At the European Society for Medical Oncology (ESMO) 2025 Annual Congress Javier C Cortés MD PhD from the Institute of Oncology in Madrid and the International Breast Cancer Centre in Barcelona reported data from the ASCENT-03 study showing that treatment with sacituzumab govitecan brought clinically meaningful benefits with toxicities that were found to be manageable. At the congress Cortés talked about the new findings with Peter Goodwin: Audio Journal of Oncology: Javier C Cortes MD PhD “[GOODWIN] Peter Goodwin here in Berlin …..……….Audio Journal of Oncology, I’m Peter Goodwin. 9:47secs ESMO ABSTRACT: LBA20 – “Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i)” Speaker: Javier C. Cortés (Barcelona, Spain) Authors: Javier C. Cortés (Barcelona, Spain), Aditya Bardia (Los Angeles, United States of America), Kevin Punie (Antwerp, Belgium), Carlos H. Barrios (Porto Alegre, Brazil), Sara A. Hurvitz (Seattle, United States of America, CA),Andreas Schneeweiss (Heidelberg, Germany), Joohyuk Sohn (Seoul, Republic of Korea), Eriko Tokunaga (Fukuoka, Japan), Adam M. Brufsky (Pittsburgh, United States of America, PA), Yeon Hee Park (Seoul, Republic of Korea), Binghe Xu (Beijing, China), Roberto Hegg (São Paulo, Brazil), Mafalda Oliveira (Barcelona, Spain), Alessandra Fabi (Rome, Italy), Natalya Vaksman (Miami, United States of America), Theresa Valdez (Miami, United States of America), Xinrui Zhang (Miami, United States of America), Catherine Lai (Foster City, United States of America, CA), Sara M. Tolaney (Boston, United States of America, MA) Background Significant PFS benefit was observed with SG vs chemo in pretreated metastatic (m)TNBC (ASCENT) and with SG + pembrolizumab vs chemo + pembrolizumab in first-line (1L) PD-L1+ mTNBC (ASCENT-04). For pts with mTNBC who cannot receive PD-(L)1i, treatment options are limited. We report primary results from the randomized phase 3 ASCENT-03 study (NCT05382299) of 1L SG vs chemo in pts with locally advanced unresectable or mTNBC who are unable to receive a PD-(L)1i. Methods Pts had centrally confirmed PD-L1− mTNBC (defined as combined positive score [CPS] < 10) or PD-L1+ mTNBC (CPS ≥ 10) but were unable to receive PD-(L)1i due to a comorbidity or prior use in the curative setting. Randomization (1:1) to SG (10 mg/kg IV, days 1 & 8 in 21-day cycles) or chemo (paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin) was stratified by disease status and geography. The primary end point was PFS by BICR. Key secondary end points included overall survival (OS), ORR and DOR by BICR, and safety. Results 558 pts (279 in each group) with mTNBC were randomized. With a median follow-up of 13.2 mo, SG showed a significant improvement in median PFS vs chemo (9.7 vs 6.9 mo; HR, 0.62; 95% CI, 0.50-0.78; P < .0001); median DOR was 12.2 mo vs 7.2 mo (Table). OS data were immature. The most frequent grade ≥ 3 TEAEs were neutropenia (43%) and diarrhea (9%) with SG and neutropenia (41%) and anemia (16%) with chemo. Conclusions SG led to a statistically significant and clinically meaningful improvement in PFS and more durable responses vs chemo in 1L mTNBC. The safety profile of SG was manageable and consistent with its known profile; treatment discontinuation rate due to TEAEs was lower with SG vs chemo. These data support SG as a potential new standard of care for pts with previously untreated mTNBC who are unable to receive a PD-(L)1i. Table: LBA20 Clinical trial identification NCT05382299. Editorial acknowledgement Editorial assistance was provided by Peggy Robinet, PharmD, PhD, and Sonal S. Joshi, PhD, of Parexel, and funded by Gilead Sciences, Inc. Legal entity responsible for the study Gilead Sciences, Inc. Funding Gilead Sciences, Inc. PRESS RELEASE: ASCENT-03: Trodelvy® Demonstrates Highly Statistically Significant & Clinically Meaningful Improvement in Progression Free Survival in Patients With First-line Metastatic Triple-Negative Breast Cancer Who Are Not Candidates for Checkpoint Inhibitors – Second Positive Phase 3 Trial in First-line Metastatic TNBC Where Trodelvy Has Demonstrated a Clinically Meaningful Benefit Versus Standard of Care Chemotherapy – – Trodelvy Has