Audio Journal of Oncology Podcast

Anti-Claudin 6 Antibody Drug Conjugate Benefits Patients with Advanced Platinum-Resistant Ovarian Cancer with Low Toxicity An interview with: Tao Zhu, MD, Chief Physician and Vice President, Zhejiang Cancer Hospital, China SAN DIEGO, USA— The investigational drug QLS5132 had “remarkable anti-tumor activity” in patients with late-stage platinum resistant ovarian cancer, according to data reported at the American Association of Cancer Research 2026 Annual Meeting. The drug is an antibody drug conjugate targeting the transmembrane protein claudin 6, which has almost no expression in healthy tissue, but is expressed in some cancer tissues, including ovarian cancer. Tao Zhu MD, chief physician and vice president of Zhejiang Cancer Hospital in China told the AACR about the encouraging response rates they noted among 28 patients with ovarian cancer, with manageable toxicities. He gave more details to our reporter, Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Tao Zhu MD IN: [GOODWIN]”I am at the AACR Meeting … OUT: ….for the Audio Journal of Oncology 4:49 AACR 2026 ABSTRACT: Presentation CT037: Publishing Title: A first-in-human phase 1 trial of a novel claudin 6 (CLDN6)-targeting antibody drug conjugate (ADC) QLS5132 in patients (pts) with platinum-resistant ovarian cancer (PROC) Author Block: Y. Xiang1, Z. Song2, J. Li3, L. Chen3, Y. Sun4, D. Zou5, Y. Li5, S. Zhang6, Y. Ding6, Y. Gu1, X. Liu7, T. Zhang7, X. Kang7, W. Tao7, T. Zhu2; Hall H – Ground Level – Convention Center 1Peking Union Medical College Hospital, Beijing, China, 2Zhejiang Cancer Hospital, Hangzhou, China, 3Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute, Shandong Cancer Hospital), Jinan, China, 4Fujian Cancer Hospital, Fuzhou, China, 5Chongqing University Cancer Hospital, Chongqing, China, 6The First Hospital of Jilin University, Changchun, China, 7Qilu Pharmaceutical Co., Ltd., Jinan, China Abstract Body: Background: QLS5132 is a highly selective ADC composed of a humanized anti-CLDN6 hIgG1 antibody and a novel topoisomerase-1 inhibitor as cytotoxic payload via a hydrophilic cleavable linker LK1b, with a drug-to-antibody ratio of 8. QLS5132 showed an expanded therapeutic window and potent antitumor activity in PROC in preclinical studies. Methods: The trial (NCT06932094) recruited pts with histologically or cytologically confirmed advanced PROC, who failed or had no standard therapy. Accelerated titration design and Bayesian optimal interval design were adopted in dose-escalation stage. QLS5132 was administered via intravenous infusion once Q3W at dose levels of 1.6 mg/kg, 3.2 mg/kg, 4.8 mg/kg, 5.6 mg/kg, and 6.4 mg/kg. Two dose levels would be selected in dose-expansion phase. The primary endpoints were safety. Results: As of Jan 21, 2026, 28 pts with advanced PROC were enrolled (ovarian cancers:26 pts, fallopian tube cancers:2 pts). The dose-escalation for the 6.4 mg/kg cohort was completed. Median age was 57.5 years. Ten (35.7%) pts received ≥5 lines of prior treatment, 25 (89.3%) pts received prior bevacizumab, and 22 (78.6%) pts received prior polyADP ribose polymerase inhibitors. Dose-limiting toxicity of grade 4 platelet count decreased occurred in one patient at 6.4 mg/kg dose level. Twenty-six (92.9%) pts experienced TEAEs (treatment-related, 92.9%). The most common TRAEs of any grade with incidence >50% were nausea (85.7%), anorexia (60.7%), anemia (53.6%), and weakness (53.6%). Alopecia, bone pain, back pain, hypoesthesia, and mucositis oral occurred in one (3.6%) patient, respectively. No interstitial lung disease, ocular toxicity, or febrile neutropenia occurred. Most gastrointestinal TRAEs were grade 1 or 2. Nine (32.1%) pts experienced grade ≥3 TRAEs. The hematological TRAEs of grade ≥3 occurred in 2 (66.7%) pts at 6.4 mg/kg dose level, and 5 (20.0%) pts at <6.4 mg/kg dose level. TRSAEs occurred in one (3.6%) patient at 6.4 mg/kg dose level, which were hematologic toxicities. There we

New Generation KRAS G12C Inhibitor Brings Promising Responses Even in Patients with Advanced Lung Cancers Refractory to Previous KRAS-targeted Therapy An interview with Byoung Chul Cho MD PhD, Thoracic Medical Oncologist, Professor, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. SAN DIEGO, USA—In a phase 1/2 study in which patients with advanced non-small cell lung cancer were treated with the next-generation KRAS-G12C inhibitor elisrasib, responses were seen not only in patients who were not treated with prior KRAS G12C inhibitors but also in those whose disease progressed on prior KRAS G12C inhibitors. Study findings were reported at the 2026 Annual Meeting of the American Association for Cancer Research by Byoung Chul Cho MD PhD, a professor and thoracic medical oncologist at the Yonsei Cancer Center, in Yonsei University College of Medicine, Seoul, South Korea. He discussed his findings with our reporter Peter Goodwin. PODCAST: Byoung Chul Cho MD PhD IN: [GOODWIN]”I’m here at the American OUT:…….for Cancer Research. I’m Peter Goodwin 7:58secs AACR 2026 abstract: Session Type: Clinical Trials Plenary Session Session Title: New Frontiers in Precision Oncology Presentation CT020 Publishing Title: Safety and efficacy of Elisrasib (D3S-001), a next generation GDP-bound KRAS G12C inhibitor, as monotherapy in advanced non-small cell lung cancer (NSCLC) previously treated with or without a KRAS G12C inhibitor: Results from a phase 1 / 2 study Authors: Byoung Chul Cho1, Shun Lu2, Ziming Li2, John Park3, Jun Zhao4, Herbert Ho Fung Loong5, Antoine Hollebecque6, Bin Yang7, Binchao Wang8, Cheng Chen9, Jia Wang9, Shaonan Wang9, Yandong Shen9, Zifei Fan9, Qian Chen9, Hui Wang9, Jing Zhang9, George Zhi Jian Chen9, Melissa Johnson10, Tony Shu Kam Mok5 1Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of, 2Department of Medical Oncology, Shanghai Chest Author Block: Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China, 3Macquarie Medical School, Macquarie University, Sydney, Australia, 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China, 5The Chinese University of Hong Kong, Hong Kong, China, 6Gustave Roussy, Villejuif, France, 7Hubei Cancer Hospital, Hubei, China, 8Guangdong General Hospital- Huifu Branch, Guangzhou, China, 9D3 Bio Inc., Shanghai, China, 10Sarah Cannon Research Institute, Nashville, TN Background: Elisrasib is a next-generation KRAS-G12C inhibitor (G12Ci) designed to improve target engagement (TE) efficiency and overcome growth factor-induced nucleotide exchange. This unique MoA distinguishes elisrasib from first-generation G12Ci and has led to robust anti-tumor activity in G12Ci-naïve/-resistant PDX models. Ph1 results demonstrated favorable safety and promising efficacy across NSCLC, CRC and PDAC. Here, we present updated findings in previously treated locally advanced or metastatic NSCLC patients (pts) (naïve and refractory to G12Ci) from the ongoing Ph1/2 trial (NCT05410145). Methods: Pts with locally advanced or metastatic KRAS G12C-mutated NSCLC were eligible. All pts must had received at least one prior line of systemic treatment, including IO and/or platinum doublet chemotherapy. For G12Ci-refractory pts, they were required to have radiologically or clinically documented PD following a KRAS G12Ci. Elisrasib was administered orally QD in 21-day cycles at 6 planned dose levels (50-900mg) in the dose escalation and 600mg was selected as the treatment dose for expansion cohorts. The key objectives included safety, efficacy, and ctDNA kinetics by liquid biopsy (Guardant360® CDx or OncoCompass® Target). Results: As of 06 Jan 2026, total 165 NSCLC pts across 9 countries received elisrasib monotherapy (2 in 50mg, 5 in 100mg, 4 in 200mg, 6 in 400mg, 144 in 600mg and 4

Safe to Avoid Endocrine Therapy in Older Women with Low Risk Breast Cancers: EUROPA Study Interim Findings An interview with: Icro Meattini MD, Associate Professor of Radiotherapy, University of Florence, Clinical Oncologist, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Italy BARCELONA, Spain—More evidence has emerged showing that older women with breast cancers that are not life threatening can safely receive only radiotherapy after breast conserving therapy, without adding hormone treatments. At the 2026 European Breast Cancer Conference emerging findings from the EUROPA study of women over 70 with “luminal-like” early breast cancer were discussed by Icro Meattini MD, Associate Professor of Radiotherapy at the University of Florence, and Clinical Oncologist at Azienda Ospedaliero-Universitaria Careggi, University of Florence, Italy. He talked with Peter Goodwin about the findings and clinical implications: AUDIO JOURNAL OF ONCOLOGY: Iccro Mettini MD IN: [GOODWIN]”Peter Goodwin here in Barcelona….. OUT: ….. of Oncology, I’m Peter Goodwin 2026 European Breast Cancer Conference: “EUROPA Study: Endocrine or Radiation Therapy for Elderly Patient with Small Early Breast Cancers, Luminal A-like” (Follow up from SABCS interim findings report (2024)) DETAILS: At SABCS 2024, Dr. Icro Meattini presented a preplanned interim analysis of the EUROPA trial, a randomized phase III study comparing exclusive endocrine therapy (ET) vs. radiation therapy (RT) in women aged 70+ with luminal-like early breast cancer. The study aimed to evaluate quality of life (HRQOL) and ipsilateral breast tumor recurrence (IBTR) to guide treatment decisions in this patient population. Key Findings: RT preserved HRQOL scores better than ET at 24 months (mean change: -3.4 RT vs. -9.79 ET, p=0.045). Treatment-related adverse events (AEs) were lower in the RT arm (67%) compared to the ET arm (85.4%). No significant differences in IBTR rates at this interim analysis, but longer follow-up is needed for definitive conclusions. RT showed better functional outcomes compared to ET across multiple QLQ-C30 domains Clinical Implications: These results suggest that both RT and ET may be viable single-modality treatment options in this population, with HRQOL and toxicity profiles playing a key role in treatment selection. The study underscores the importance of multidisciplinary, patient-centered approaches in older women with early-stage breast cancer. 2024 EUROPA Findings: Looking back at SABCS 2024, the EUROPA trial continues to provide valuable insights into optimizing treatment decisions for older breast cancer patients. SABCS PAPER (Lancet Oncology): 00661-2/abstract Single-modality endocrine therapy versus radiotherapy after breast-conserving surgery in women aged 70 years and older with luminal A-like early breast cancer (EUROPA): a preplanned interim analysis of a phase 3, non-inferiority, randomised trial Icro Meattini, MDa,b icro.meattini@unifi.it ∙ Maria Carmen De Santis, MDc ∙ Luca Visani, MDb ∙ Prof Marta Scorsetti, MDd ∙ Alessandra Fozza, MDe ∙ Bruno Meduri, MDf ∙ et al. Show more Background Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population. Methods This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre). Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy. En

Radiation Boost May No Longer Be Justified After Standard Therapy for Early Breast Cancer An interview with: Eline Verreck BSc, Erasmus University Medical Centre, Surgical Oncology Department, Rotterdam, The Netherlands BARCELONA, Spain—Any benefit from an additional tumor-bed radiotherapy “boost” after completing standard therapy for early breast cancer seems no longer to be justified in this age of increasingly effective systemic treatments now being incorporated into standard breast-conserving therapy. A new study conducted in the Netherlands, with 34,504 patients followed up for a median of 8.3 years, has found that the possible small reductions of long-term local recurrence rates from using a boost no longer justify the toxicities such a boost can bring. Findings were reported at the 2026 meeting of the European Breast Cancer Conference by Eline Verreck BSc, who is a PhD candidate at Erasmus University Medical Centre’s Department of Surgical Oncology in Rotterdam. She talked about her results with the Audio Journal of Oncology’s correspondent, Peter Goodwin: AUDIO J0URNAL OF ONCOLOGY: Eline Verreck BSc IN: [GOODWIN]” Welcome to more news here from the ….. OUT: …….I’m Peter Goodwin for the Audio Journal of Oncology 7:00secs EBCC 2026 ABSTRACT PPT-054 “The relevance of a boost in the current era of systemic therapy after breast-conserving surgery and radiotherapy” Verreck1,, W.D. Heemsbergen2,, T. van Dalen3,, S. Windhorst4,, L. de Munck4,, F. van der Leij5,, L.J. Boersma6,, F.E. Froklage2,. 1Erasmus University Medical Centre, Surgical Oncology, Rotterdam, The Netherlands. 2Erasmus University Medical Centre, Department of Radiation Oncology, Rotterdam, The Netherlands. 3Erasmus University Medical Centre, Department of Surgical Oncology, Rotterdam, The Netherlands. 4Netherlands Comprehensive Cancer Organisation, Department of Research and Development, Utrecht, The Netherlands. 5University Medical Centre Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands. 6Grow Research Institute for Oncology and Reproduction- Maastricht University Medical Centre+, Department of Radiation Oncology Maastro, Maastricht, The Netherlands. Background: Breast-conserving surgery (BCS) is commonly followed by whole breast radiotherapy (WBRT), which may include a boost to the tumour bed. The former boost trial (Bartelink, 2015) showed a 50% reduction in local recurrence (LR) risk. However, systemic therapy has evolved substantially since then, resulting in an absolute LR risk of <5% at 10 years. In the current era, a boost may therefore represent overtreatment. Moreover, it is associated with increased fibrosis risk and poorer cosmetic outcomes. The Assisi Think Tank Meeting 2024 suggested omission of a boost in patients whose 10-year LR risk without a boost is <6%. Therefore, this study aims to identify patients with a 10-year LR risk of <6% after WBRT without a boost, and patients with a 10-year LR risk of <3% after WBRT with a boost. Methods: This study included all Dutch breast cancer (BC) patients treated with BCS and adjuvant WBRT between 2012-2016. Data were obtained from the Netherlands Cancer Registry, and information on LR was collected through linkage with PALGA, the nationwide pathology database. Using this methodology, LR data completeness is estimated to be approximately 80% (van Maaren, 2025). The LR risk was described for patients treated without and with boost, and for subgroups defined by known risk factors within these two categories. Results: A total of 34,504 patients with a median follow-up of 8.3 years were included. Four percent were ≤40 years old, 23% had grade 3 tumours, 11% had triple-negative BC, and 6% had focally positive margins, with 90%, 82%, 75%, and 87% of each group receiving a boost, respectively. (Neo)adjuvant systemic therapy was administered to 64% of patients (39% chemotherapy +/- targeted therapy, 52% endocrine therapy). LR occurred in 343 patients (1.0%), of whom 174 (51%) ha

‘Lord’ Trial Finds Active Surveillance for Estrogen-Receptor-Positive, HER2-Negative, Grade 1–2 DCIS Just As Effective as Standard Therapy An interview with: Jelle Wesseling MD PhD, Pathologist, Medical Director, Early Cancers Detection Centre, Netherlands Cancer Institute, Division of Molecular Pathology, Amsterdam, The Netherlands. BARCELONA, Spain: Because low-risk ductal carcinoma in situ (DCIS) is often unlikely to progress to breast cancer, de-escalating therapy was on the agenda of the Lord trial of active surveillance, that was reported at the 2026 European Breast Cancer Conference. The findings were reassuring: So much so that randomization was stopped early. The lead study author, pathologist Jelle Wesseling MD PhD who is Medical Director of the Early Cancers Detection Centre at the Netherlands Cancer Institute in Amsterdam, gave the details to the Audio Journal of Oncology’s Peter Goodwin. AUDIO JOURNAL OF ONCOLGY: Jelle Wesseling MD PhD IN: [GOODWIN]” I am at the European Breast …. OUT: ….of Oncology, I’m Peter Goodwin 10:34secs EBCC 2025 Abstract no: 2LBA: “De-escalating treatment for low-risk Ductal Carcinoma In Situ: early safety of active surveillance without endocrine therapy in the prespecified interim analysis of the LORD-trial* (BOOG 2014-04)” Authors: Wesseling1,2,3,4, M. Nieberg1, S. Aleikhaneshir1, L. Elshof1, R. Schmitz1, C. Sondermeijer5, S. Balduzzi5, K. Pengel5, J. Weiner1, M. Gerritsma6, E. Engelhardt6, E. Bleiker6, E. Verschuur7, I. Langerak8, R. Mann9, E. van Leeuwen-Stok10, E. Lips1, N. Bijker11, F. van Duijnhoven12 1The Netherlands Cancer Institute, Division of Molecular Pathology, Amsterdam, The Netherlands 2Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands 3 The Netherlands Cancer Institute, Center of Early Cancer Detection, Amsterdam, The Netherlands 4The Netherlands Cancer Institute, Department of Pathology, Amsterdam, The Netherlands 5The Netherlands Cancer Institute, Biometrics Department, Amsterdam, The Netherlands 6The Netherlands Cancer Institute, Division of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands 7Europa Donna & Dutch Breast Cancer Patient Association BVN, Patient Advocacy, Utrecht, The Netherlands 8Dutch Breast Cancer Patient Association BVN, Patient Advocacy, Utrecht, The Netherlands 9The Netherlands Cancer Institute, Department of Radiology, Amsterdam, The Netherlands 10BOOG Study Center, National Breast Cancer Trial Coordination, Utrecht, The Netherlands 11The Netherlands Cancer Institute, Depratment of Radiation Oncology, Amsterdam, The Netherlands 12The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, The Netherlands Background Active surveillance has been proposed as a de-escalation strategy for women with low-risk ductal carcinoma in situ (DCIS). The LORD-trial evaluates the safety of active surveillance compared with standard treatment in women with estrogen-receptor-positive, HER2- negative, grade 1–2 DCIS. Methods The LORD-trial is a multicentre study that followed a patient-preference design after initial randomization proved infeasible. The primary endpoint is ipsilateral invasive breast cancer (iiBC)-free rate at 10 years. A prespecified, non-binding interim futility analysis was planned after 60 iiBC events. Results DSMB prespecified interim analysis 1,423 women had been enrolled with a median follow-up of 23 months. The first n=73 were randomized between the two arms. After transforming to a patient preference design, n=1,025 patients opted for active surveillance and n=330 for standard treatment. No patients received endocrine therapy. On an intention-to-treat basis, iiBC occurred in 4/363 (1%) women allocated to standard treatment and 63/1,060 (6%) women undergoing active surveillance. Based on these findings, the Data Safety Monitoring Board (DSMB) advised cessation of registration and recruitment, while continuing follow-up of enrolled patients. Cohort analysis When iiBCs

Polyurethane-Coated Implants Reduce Capsular Contracture Risk after Mastectomy with Radiotherapy for Breast Cancer An interview with: Kerstin Wimmer MD, Medical University of Vienna, Department of General Surgery, Vienna, Austria; Post-Doctoral Researcher, Karolinska Institute, Stockholm, Sweden BARCELONA, Spain—Women who had mastectomy with immediate pre-pectoral breast reconstruction followed by radiotherapy had less risk of capsular contracture when polyurethane-coated breast implants were used rather than un-coated implants. This finding from the OPBC-09 PRExRT study was reported at the 2026 European Breast Cancer Conference by Kerstin Wimmer MD, from the Medical University of Vienna’s Department of General Surgery in Vienna, Austria, who is currently doing post-doctoral researcher at the Karolinska Institute in Stockholm, Sweden. After her presentation, she discussed the findings with Audio Journal of Oncology correspondent Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Kerstin Wimmer MD IN: [GOODWIN]”Peter Goodwin here, reporting…… OUT: on Oncology, I’m Peter Goodwin 2026 EBCC: Barcelona Abstract no: 2 The impact of polyurethane coated implants on the risk of capsular contracture after immediate prepectoral breast reconstruction in the setting of postmastectomy radiotherapy: the OPBC-09 PRExRT study Wimmer1, R. Kiblawi2, F. Fitzal3, C. Kohl4, L. Stenman Skarsgård5, G. Franceschini6, D. Virzi7, Molska8, J.M. Broyles9, A. Agrawal10, G. Montagna11, M. Rivas Ibarra12, M. Banys-Paluchowski13, M. Knauer14, E. Gonzales15, J. Letzkus Berrios16, G. Karadeniz Çakmak17, D. Vorburger18, Ferrucci19, W.P. Weber20 OPBC study group 1Medical University of Vienna, Department of General Surgery, Vienna, Austria 2University Hospital Basel, Department of Gynaecology & Obstetrics, Basel, Austria 3Hanusch Hospital, Department of Breast Reconstruction, Vienna, Austria 4Kliniken Essen-Mitte, Interdisciplinary Breast Center, Essen, Germany 5Oslo University Hospital, Department of Plastic and Reconstructive Surgery, Oslo, Norway 6Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Department of Science and Health of Women- Children and Public Health, Rome, Italy 7Humanitas Istituto Clinico Catanese, Plastic Surgery Unit, Catania, Italy 8University Hospital Zielona Góra, Clinical Department of General and Oncological Surgery, Zielona Góra, Poland 9Dana Farber/Brigham Cancer Center, Division of Breast Surgery- Brigham and Women’s Hospital, Boston, USA 10Cambridge University Hospitals, Department of Breast Surgery, Cambridge, United Kingdom 11Memorial Sloan Kettering Cancer Center, Breast Service- Department of Surgery, New York, USA 12Arturo López Pérez Foundation, Department of Breast Surgery, Santiago, Chile 13University Hospital Schleswig-Holstein- Campus Lübeck, Department of Gynecology and Obstetrics, Lübeck, Germany 14Tumor and Breast Center Eastern Switzerland, Tumor and Breast Center, St.Gallen, Switzerland 15Sanatorio Modelo Quilmes, Department of Senology, Buenos Aires, Argentina 16San Borja Arriarán Clinical Hospital-Clínica MEDS, Breast Surgical Unit, Santiago, Chile 17Zonguldak Bülent Ecevit University Faculty of Medicine, Department of General Surgery, Zonguldak, Turkey 18University Hospital Zurich, Breast Cancer Center- Department of Gynecology, Zurich, Switzerland 19IRCCS, Veneto Institute of Oncology, Padova, Italy 20University Hospital Basel, Breast Clinic, Basel, Switzerland Introduction Patients with breast cancer undergoing mastectomy with implant-based breast reconstruction (IBBR), who are at high risk of locoregional recurrence, often require postmastectomy radiotherapy (PMRT), which increases the risk of capsular contracture (CC). The present study assessed the association between use of polyurethane coated (PUc) versus non-PUc implants and the need for surgical revision due to CC in the setting of PMRT. Material and methods This international multicenter retrospective real-world study included patients with

BRAVE-HEART Study Shows How Breath-Holding System Halves Coronary Radiation Dose During Left Breast Irradiation An interview with: Elisabetta Bonzano MD PhD, IRCCS San Matteo Polyclinic Foundation, Radiation Oncology, Pavia, Italy BARCELONA, Spain—A system known as Active Breathing Co-ordination had a large, consistent and significant effect in reducing radiation dose to the heart and left anterior descending coronary artery in the BRAVE HEART study led by radiation oncologists from Pavia in Italy. Elisabetta Bonzano MD PhD, IRCCS San Matteo Polyclinic Foundation, Radiation Oncology, Pavia, Italy reported her group’s findings at the 2025 European Breast Cancer Conference. Afterwards she talked about more of the details for this edition of the Audio Journal of Oncology: AUDIO JOURNAL OF ONCOLOGY: Elisabetta Bonzano MD PhD IN: [GOODWIN]” Peter Goodwin here at the…. OUT: ………of Oncology, I’m Peter Goodwin. 5: 54 secs EBCC Presentation number:PB-008 Abstract title: BRAVE-HEART: Clinical and dosimetric validation of Active Breath Control for cardiac sparing in breast cancer radiotherapy Bonzano1,, L. Squillace1,, A. Lancia1,, J. Saddi1,, S. Colombo1,, S. La Mattina1,, D.A. Santos1,, P. Pedrazzoli2,. 1IRCCS San Matteo Polyclinic Foundation, Radiation Oncology, Pavia, Italy. 2IRCCS San Matteo Polyclinic Foundation, Oncology, Pavia, Italy. Background: Cardiac exposure during left-sided breast cancer (LBC) radiotherapy remains a key determinant of long-term morbidity and mortality. The BRAVE-HEART trial explores the clinical and dosimetric impact of Deep Inspiration Breath Hold (DIBH) using the Active Breathing Coordinator (ABC) system. This analysis quantifies the cardiac-sparing effect of ABC versus free-breathing (FB) across three fractionation schedules, validates its intrinsic benefit through intra-patient paired replanning, and assesses real-world feasibility. (ClinicalTrials.gov awaiting release) Methods: This ambispective single-center study included 400 patients with early or locally advanced LBC treated with 26 Gy/5 fx, 40 Gy/15 fx, or 50 Gy/25 fx ± SIB. Dosimetric parameters were extracted for the heart and LAD (Dmean, Dmax). Statistical analyses used the Shapiro–Wilk, Mann–Whitney U, and Wilcoxon tests; effect size was reported as Cohen’s d. Model-based estimation of cardiac mortality risk (NTCP) was performed for the replanning subgroup using the Gagliardi relative-seriality model. For this subgroup, paired FB and ABC-DIBH plans were generated on separate CT scans. Breath-hold performance (hold duration, threshold volume) was recorded to evaluate feasibility. The study was approved by the Ethics Committee of the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Results: ABC significantly reduced cardiac and LAD exposure across all fractionations (all p < 0.001), with large effect sizes (Cohen’s d ≥0.8) indicating a strong clinical impact (Tab. 1). In intra-patient replanning, ABC confirmed its dosimetric superiority over FB (p < 0.05). Model-based NTCP for late cardiac mortality showed a halving of predicted cardiac risk with ABC (0.04 vs 0.08, p < 0.001). Breath-hold metrics confirmed high feasibility (mean DIBH ≈ 25 s; threshold ≈ 1.4 L), including in elderly patients (mean age 75 years). Conclusions: ABC-assisted DIBH consistently and significantly reduced cardiac and coronary exposure across all dose regimens, with high reproducibility and feasibility. Model-based NTCP and intra-patient replanning analyses demonstrate a clinically and biologically relevant reduction in predicted long-term cardiac mortality, confirming ABC-DIBH as a reliable strategy to improve cardiac safety in left-sided breast cancer radiotherapy. Elisabetta Bonzano MD PhD

Molecular Test Distinguishes Ipsilateral Second Primary from Recurrent Breast Cancer An interview with: Tess Snellen MD, Netherlands Cancer Institute – Antoni van Leeuwenhoek hospital, Department of Surgical Oncology, Amsterdam, The Netherlands. BARCELONA, Spain—A molecular test using next generation sequencing has proved able to distinguish swiftly, and with great accuracy, the recurrence of a patient’s ipsilateral breast cancer from a completely new primary tumor. The 2026 European Breast Cancer Conference heard findings from researcher Tess Snellen from the Netherlands Cancer Institute in Amsterdam, who then talked with our reporter, Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: Tess Snellen MSc EBCC 2026 ABSTRACT: Distinguishing True Recurrence from Second Primary Breast Cancer by Molecular Clonality Analysis Snellen1,, E. Lips2,, L. Bosch3,, T. Wiersma4,, A. Scholten4,, M. Noë5,, M.J. Vrancken Peeters6,, V. Dezentjé7,. 1Netherlands Cancer Institute – Antoni van Leeuwenhoek hospital, Department of Surgical Oncology, Amsterdam, The Netherlands. Background A second breast cancer (BC) in the ipsilateral breast or regional lymph nodes may be a true recurrence (TR) or second primary (SP) tumor. This distinction is clinically relevant, as TRs are associated with a poorer prognosis and require a more challenging therapeutic approach compared to SPs. The aim of this study was to describe the findings and success rates of molecular clonality analysis (MCA) techniques used to distinguish a second ipsilateral BC as either a TR or a SP. In addition, a comparison between a MCA-based and a clinicopathological classification was made. Material and methods Through electronic patient files and pathology reports, data were collected from a historical cohort of patients who underwent MCA for a second ipsilateral locoregional BC at the Netherlands Cancer Institute between 2000 and 2024. The primary objective was to describe the findings and success rates of the different MCA techniques. The secondary objective was to compare molecular with clinicopathological classification using the Jobsen Morphology method. Results In total, 85 patients were included, in whom 99 MCAs were performed. Before 2017, all MCA involved loss of heterozygosity (LOH) analysis (100%), hereafter, targeted next-generation sequencing (NGS) panel analysis and copy number variation (CNV) analysis were introduced. After 2017, targeted NGS panel analysis was most frequently applied (65.4%), followed by CNV (18.5%) and LOH analysis (16.0%). CNV analysis had the highest success rate (93.3%) yielding the most conclusive MCA results, followed by targeted NGS panel (73.6%), and LOH analysis (61.3%) (table 1). Of the 99 MCAs, 40.4% tumor pairs were classified as clonally related, 10.1% as likely clonally, 22.2% as not clonally related, 27.3% were inconclusive. A substantial discordance (29.6%) was observed between the MCA-based classification and Jobsen Morphology method, with clinicopathological assessment showing limited predictive value for MCA-determined TRs (PPV 78.7%, NPV 22.2%). Conclusion In conclusion, we demonstrate that MCA, especially targeted NGS panel and CNV analysis, is successful in distinguishing TRs from NPs. Clinicopathological classification using the Jobsen Morphology method however has limited value in predicting clonal relatedness. Therefore, we recommend implementing MCA in the diagnostic workup of second ipsilateral BC when the outcome may influence therapeutic decision-making, as part of a tailored treatment approach for BC recurrence. 260325 Tess Snellen EBCC 2026 Audio Journal of Oncology

Hope S. Rugo, MD; SABCS 2025: Selective Estrogen Degrader Giredestrant Brings Clinically Meaningful Improvements in Metastatic Breast Cancer: evERA Breast Cancer Trial An interview with: Hope S. Rugo, MD, Director, Women’s Cancers Program; Division Chief, Breast Medical Oncology; Professor, Department of Medical Oncology and Therapeutic Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA SAN ANTONIO, USA—Further improvements in hormone therapy for ER-positive breast cancer were on display at the San Antonio Breast Cancer Symposium where results from the Phase III evERA Breast Cancer trial were discussed. The study investigated the use of the selective estrogen degrader agent giredestrant used together with everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancers that had previously been treated with a CDK4/6 inhibitor. Hope S. Rugo, MD, Division Chief of Breast Medical Oncology at the City of Hope Comprehensive Cancer Center in Duarte, California, delivered the latest findings at the conference. Afterwards she talked with Peter Goodwin from the Audio Journal of Oncology. Audio Journal of Oncology: Hope S. Rugo IN: [GOODWIN]”Peter Goodwin here with the …. OUT: …..thank you so much! Bye! 11:40 secs San Antonio Breast Cancer Symposium, Abstract GS3-09: Clinical and biomarker subgroup analysis of evERA Breast Cancer: A Phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor. S. Rugo; S. M. Tolaney; K. L. Jhaveri; M. Martin; G. A. Vidal; L. Moscetti; A. Brufsky; W. J. Gradishar; A. Schneeweiss; N. Niikura; A. Favret; M. Alfie; K. S. Lee; S. Khan; M. Feldman; B. M. Day; L. H. Lam; W. C. Darbonne; T. M. Fernando; P. Perez-Moreno; E. L. Mayer Background The first-line standard of care (SOC) for patients (pts) with estrogen receptor-positive, HER2-negative advanced breast cancer (ER+, HER2- aBC) is CDK4/6 inhibitor (i) + endocrine therapy (ET) but effective post-CDK4/6i options remain limited. Giredestrant (GIRE) targets the ER pathway while everolimus (E) targets the PI3K/AKT/mTOR pathway; both of which are implicated in driving resistance in the post-CDK4/6i setting. evERA BC (NCT05306340) is the first Phase III trial to demonstrate statistically significant and clinically meaningful improvement in investigator-assessed progression-free survival (INV-PFS) with an all-oral selective ER antagonist and degrader combination of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET, both in pts whose tumors had a detectable ESR1 mutation (m) and in the intent-to-treat (ITT) population (Mayer ESMO 2025). The safety profile of GIRE + E was manageable with no unexpected findings (Mayer ESMO 2025). We report results from prespecified exploratory subgroup analyses. Methods Pts who had ER+, HER2- aBC with disease progression (PD) post-CDK4/6i + ET in the aBC setting, or relapse during/after CDK4/6i + ET in the adjuvant setting, were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane, fulvestrant, or tamoxifen) + E until PD or unacceptable toxicity. Mutational status was determined using circulating tumor DNA at baseline. The co-primary endpoints were INV-PFS per Response Evaluation Criteria in Solid Tumors v1.1 in pts whose tumors had detectable ESR1m and in the ITT population. INV-PFS was assessed by subgroup analyses. Results Three-hundred-and-seventy-three pts were randomized; 183 pts were randomized to GIRE + E and 190 to SOC ET + E. A total of 207 pts (55%) had tumors with ESR1m, 115 (31%) had PIK3CAm, and 137 (37%) had alterations (alt) in the PI3K pathway genes (PIK3CA/AKT1/PTEN). Sixty-four pts (17%) had both ESR1m and PIK3CAm; 76 (20%) had both ESR1m and PIK3CA/AKT1/PTEN alt. Ninety-eight percent of pts received a CDK4/6i in the metastatic setting. INV-PFS benefit was observed for GIRE + E vs SOC

Juan Du MD PhD, ASH 2025: Dual Targeted FasTCAR-T Therapy brings Deep, Durable Responses to Patients with Newly Diagnosed Multiple Myeloma An interview with: Juan Du MD PhD, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China ORLANDO, USA—Patients with newly diagnosed multiple myeloma had deep, long lasting responses to initial therapy with a new CAR T-cell therapy targeting both B-cell maturation antigen (BCMA) and CD19 using the “FasTCAR-T” platform being tested in a phase one study. Lead author Juan Du MD PhD, from Ren Ji Hospital, and Jiao Tong University School of Medicine, in Shanghai, China reported early findings to the 2025 Annual Meeting of the American Society of Hematology. Afterwards she met up with the Audio Journal of Oncology’s Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY, Juan Du MD PhD https://ashpublications.org/blood/article/146/Supplement%201/258/548757/A-dual-targeting-BCMA-and-CD19-fastcar-t-GC012F A dual targeting BCMA and CD19 fastcar-t (GC012F/AZD0120) as first-line therapy for newly diagnosed multiple myeloma REFERENCE: Blood (2025) 146 (Supplement 1): 258. AUTHORS: Juan Du, Wanting Qiang, Jing Lu, Yanchun Jia, Haiyan He, Jin Liu, Pei Guo, Ying Yang, Zhongyuan Feng, Lina Jin, Xiaoqiang Fan, Nina Shah, Qi Zhang, Lianjun Shen, Jia Liu ASTRACT: Background GC012F/AZD0120 is an autologous CAR-T therapy that targets both B cell maturation antigen (BCMA) and CD19. It is developed using the novel FasTCAR-T platform, which allows for next-day manufacturing. GC012F/AZD0120 has demonstrated deep and durable responses with a manageable safety profile in relapsed/refractory multiple myeloma (RRMM) patients (pts). We conducted two phase 1, open-label, investigator-initiated trials (NCT04935580, NCT05840107) to evaluate safety and efficacy of GC012F/AZD0120 in newly diagnosed multiple myeloma (NDMM) pts, including transplant eligible high risk (TE HR) NDMM and transplant ineligible (TI) NDMM. Here, we report the combined data of these two studies to provide long term follow up data of GC012F/AZD0120 in NDMM pts. Methods Eligible NDMM pts received a single infusion of GC012F/AZD0120 following two cycles lenalidomide, bortezomib and dexamethasone (RVd) induction therapy. Leukapheresis was performed before induction therapy, or after 1 or 2 cycles of induction therapy. GC012F/AZD0120 was administered at 4 dose levels: 1×105/kg (n=1), 1.5×105/kg (n=3), 2×105/kg (n=4), or 3×105/kg (n=22) after a standard 3-day lymphodepletion regimen of fludarabine and cyclophosphamide. Lenalidomide maintenance was permitted to be administered post infusion per investigator’s discretion. Results As of June 3, 2025, a total of 30 patients were infused and evaluable. The median age was 64 years (range, 43-78), with 27% aged over 70 years. 19 pts (63%) were male. 25 pts (83%) had R-ISS stage II/III and 14 of 29 pts (48%) had high risk cytogenetics (dep (17p), amp (1q21), t (4;14), t (14;16)). 17 pts (57%) had plasmacytomas, and 3 of them had soft tissue plasmacytomas. 29 pts (97%) received 2 cycles of RVd induction therapy prior to CAR-T infusion. The overall response rate (ORR) was 100%, and the stringent complete response (sCR) rate was 97%. The median time to first response was 28 days and the median time to best response was 68 days. All treated pts (100%) across all dose levels achieved minimal residual disease (MRD) negativity, as assessed by Euroflow (sensitivity of 10-6). Among MRD evaluable pts, MRD negativity reached 100%, 93% and 92% at Month 1, Month 6 and Month 12, respectively. 81.5% (22/27) pts’ MRD negativity sustained more than 12 months. With a median follow-up of 30 months (range, 13-47), the median progression-free survival (PFS) and overall response (OS) have not been reached. The 30-month PFS rate was 88% (95% CI 67–96) and 30-month OS rate was 92% (95% CI 71–98). For 3 soft tissue plasmacytomas pts, the median PFS was 17.9 months and t

María-Victoria Mateos; ASH 2025: Unprecedented Survival Benefits with BCMA/CD3 Bispecific Antibody Teclistamab in Patients with Relapsed or Refractory Multiple Myeloma: Majestec-3 Study Findings An interview with: María-Victoria Mateos MD PhD, Hematologist and Myeloma Unit Director, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, and Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain. ORLANDO, USA—Statistically significant improvements in progression-free and overall survival among patients with relapsed or refractory multiple myeloma were reported at the 2025 Annual Meeting of the American Society of Hematology. The addition of the B-cell maturation antigen/CD3 bispecific antibody teclistamab to standard second-line therapies, brought “clinically remarkable” benefits in the majestec-3 study. The first author María-Victoria Mateos MD PhD, Hematologist and Myeloma Unit Director at the University Hospital of Salamanca in Spain, gave the details to Audio Journal of Oncology reporter, Peter Goodwin: AUDIO JOURNAL OF ONCOLOGY: María-Victoria Mateos MD PhD IN: [GOODWIN] “Peter Goodwin here at the American ……. OUT: …..I’m Peter Goodwin 8:01 secs From: ASH 2025 Publication Number: LBA-6 Abstract Title : Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3 https://ashpublications.org/blood/article/146/Supplement%202/LBA-6/556932/Phase-3-randomized-study-of-teclistamab-plus María-Victoria Mateos 1Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain Blood (2025) 146 (Supplement 2): LBA-6. https://doi.org/10.1182/blood-2025-LBA-6 AUTHORS: María-Victoria Mateos1, Nizar Bahlis2, Aurore Perrot3, Ajay Nooka4, Jin Lu5, Charlotte Pawlyn6, 7, Roberto Mina8, Gaston Caeiro9, Alain Kentos10, Vania Hungria11, Donna Reece12, Ting Niu13, Anne Mylin14,Charlotte Hansen15, Raphael Teipel16, Britta Besemer17, Meletios Dimopoulos18, 19, Elena Zamagni20, 21, Satoshi Yoshihara22, Kihyun Kim23, Chang-Ki Min24, Paulus Geerts25, Elena Van Leeuwen-Segarceanu26, Agata Tyczynska27, Juan Luis Reguera28, Magnus Johansson29, Markus Hansson30, Mehmet Turgut31,Mark Grey32, Surbhi Sidana33, Paula Rodriguez-Otero34, Joaquin Martinez-Lopez35, Hamza Hashmi36, Robin Carson37, Rachel Kobos38, Weili Sun39, Kristen Lantz37, Anne Seifert40, Debbie Briseno-Toomey41, Lisa O’Rourke37, Maria Rubin38, Diego Vieyra37, Lijuan Kang39, Luciano Costa42 INSTITUTIONS 1 Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain, 2 Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, 3 Universite de Toulouse, Centre Hospitalier Universitaire, Service d’Hematologie, IUCT Oncopole CRCT, Toulouse, France, 4 Emory University, Winship Cancer Institute, Atlanta, GA, United States, 5 Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China, 6 The Royal Marsden NHS Foundation Trust, London, United Kingdom, 7 The Institute of Cancer Research, London, United Kingdom, 8 Division of Hematology, Department of Molecular Biotechnology and Health Sciences, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy, 9 Hospital Privado Centro Medico de Córdoba SA, Córdoba, Argentina, 10 Department of Hematology, Hôpital de Jolimont,

Wojciech Jurczak MD PhD; ASH 2025: Big Study Suggests Non-Covalent BTK Inhibitor Pirtobrutinib Could be New Standard-of-Care for Patients with Untreated Chronic Lymphocytic Leukemia An interview with: Wojciech Jurczak MD PhD, Professor of Hematology, National Research Institute of Oncology, Krakow, Poland ORLANDO, USA— A non-covalent inhibitor of Bruton’s tyrosine kinase looks superior to the current standard of care as initial therapy for patients with chronic lymphocytic leukemia. That’s in research from Poland reported at the 2025 American Society of Hematology Annual Meeting in which the randomized CLL/SLL (BRUIN CLL-313; NCT05023980) phase three study compared pirtobrutinib with bendamustine plus rituximab in treatment-naïve patients. Lead author Wojciech Jurczak MD PhD, Professor of Hematology at the National Research Institute of Oncology in Krakow, Poland, has been telling the Audio Journal of Oncology’s Peter Goodwin about the results: AUDIO JOURNAL OF ONCOLOGY; Wojciech Jurczak MD PhD IN: [GOODWIN] “Peter Goodwin……. OUT: …….Peter Goodwin. 10:19 AMERICAN SOCIETY OF HEMATOLOGY ABSTRACT Number: LBA 3 Publication: https://ashpublications.org/blood/article/146/Supplement%202/LBA-3/556927/Pirtobrutinib-vs-bendamustine-plus-rituximab-BR-in STUDY TITLE: Pirtobrutinib vs bendamustine plus rituximab (BR) in patients with CLL/SLL: First results from a randomized phase III study Examining a non-covalent BTK inhibitor in untreated patients Blood (2025) 146 (Supplement 2): LBA-3. https://doi.org/10.1182/blood-2025-LBA-3 AUTHORS: Wojciech Jurczak, Michal Kwiatek, Jaroslaw Czyz, Ederson de Mattos, Ki-Seong Eom, Alexander Egle, Anna Panovská, Zhanet Grudeva-Popova, Hsuan-Jen Shih, Luis Felipe Casado Montero, Paolo Sportoletti, Vu Minh Hua, James D’Olimpio, Shinsuke Iida, Rodrigo Ito, Katherine Bao, Anne Fink, Weiji Su, Amy Ruppert Stark, Alejandro Levy, Tomasz Wrobel INSTITUTIONS: 1 National Research Institute of Oncology, Krakow, Poland, 2 AIDPORT Clinical Trials Hospital, Skorzewo, Poland, 3 Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Torun, Poland, 4 Hospital Amaral Carvalho Jau, São Paulo, Brazil, 5 Catholic Hematology Hospital, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea, Rep. of South, 6 Paracelsus University Hospital, Salzburg, Austria, 7 Masaryk University, Brno, Czech Republic, 8 Medical University of Plovdiv, Plovdiv, Bulgaria, 9 Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan, 10 HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Instituto de Investigación Sanitaria HM Hospitales, Madrid, Spain, 11 Institute of Hematology Centro di Ricerca Emato- Oncologica (CREO), University of Perugia, Perugia, Italy, 12 Liverpool Hospital, New South Wales, Australia, 13 Clinical Research Alliance, Westbury, United States, 14 Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 15 Eli Lilly and Company, Indianapolis, IN, United States, 16 Wroclaw Medical University, Wroclaw, Poland Abstract Introduction: Pirtobrutinib is a highly selective, non-covalent (nc) Bruton tyrosine kinase inhibitor (BTKi) that has demonstrated safety and efficacy in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including pts previously treated with a cBTKi. While cBTKi have significantly improved progression-free survival (PFS) for untreated pts with CLL/SLL, there are no Phase 3 data assessing a ncBTKi specifically in the treatment-naïve setting, and significant improvements in overall survival (OS) are uncommon with monotherapy cBTKi. A recent head-to-head phase 3 trial (BRUIN CLL-314 presented at this meeting, ASH abstract 25-2587; NCT05254743) showed a favorable overall response rate (ORR) and a positive PFS trend with pirtobrutinib compared to the cBTKi ibrutinib in a subset of pts with treatment-naïve CLL. Here we present the first results from a randomized, open-label, global phase 3 trial