First-Line Treatment for Metastatic TNBC: Inside the ASCENT-03 Trial | Dr. Alissa Huston, University of Rochester

This episode is sponsored by Gilead Sciences. Gilead had no involvement or input in the podcast content. Gilead is working to transform how cancer is treated. We are innovating with next-generation therapies, combinations, and technologies to deliver improved outcomes for people with cancer. From antibody drug conjugates and small molecules to cell therapy-based approaches, our portfolio and pipeline assets are creating new possibilities for people with cancer. **UPDATE SINCE RECORDING JANUARY 2026.** Since this recorded conversation, the FDA has acted on the data discussed in this episode. On May 22, 2026, Datopotamab Deruxtecan was approved for first-line metastatic TNBC in patients who are not candidates for immunotherapy. On June 24, 2026, Sacituzumab Govitecan was approved for first-line use both as a single agent and in combination with pembrolizumab for PD-L1-positive disease (CPS ≥10). Consult with your care team for the most recent indications and availability of these treatment options. **Metastatic triple-negative breast cancer has historically had the fewest targeted options of any breast cancer subtype. The ASCENT-03 trial changed the first-line picture.** ASCENT-03 (NCT05382299) was a phase 3, open-label, randomized trial of 558 patients with unresectable locally advanced or metastatic triple-negative breast cancer who had not received prior systemic therapy for advanced disease and who were not candidates for PD-1 or PD-L1 inhibitor therapy. Participants were randomized 1:1 to sacituzumab govitecan-hziy or to physician's choice of chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). 0:00 Treating cancer like a game of chess 0:44 Introducing Dr. Alissa Huston 1:11 Breast oncology and integrative oncology in one practice 2:58 Twenty years of change: from tumor size to molecular profiling 4:28 Where metastatic triple-negative breast cancer stands today 5:55 What is PD-L1, and how does immunotherapy work? 6:46 Why immune-related side effects behave differently 8:05 Choosing between immunotherapy, ADCs, and chemotherapy 9:58 Inside ASCENT-03: what the trial studied and who it enrolled 12:15 Progression-free survival, explained in plain language 16:50 What the first appointment actually looks like 19:22 Holding hope and toxicity in the same conversation 20:34 Supportive and integrative tools for managing side effects 21:29 Neutropenia, infection risk, and growth factor support 22:50 Cumulative toxicity versus emerging toxicity 25:47 Toxicity grading and why doses get reduced 26:34 Why patients hide side effects, and why dose reductions are planned 30:02 The chess analogy, revisited 32:09 One piece of advice at diagnosis 33:43 Rapid fire: ASCENT-03, progression-free survival, overall survival 36:15 Rapid fire: antibody-drug conjugates and first-line treatment 37:33 What is integrative oncology? 38:09 Closing thoughts Alissa Huston, MD is a Professor of Medicine and breast medical oncologist at the Wilmot Cancer Institute at the University of Rochester, and Co-Medical Director of the Pluta Integrative Oncology and Wellness Center. She earned her medical degree at the University of Buffalo, completed her internal medicine residency at Strong Memorial Hospital, and completed her hematology and oncology fellowship at the University of Pittsburgh. Her research focuses on the effects of breast cancer treatment on bone health and on evidence-based integrative approaches to symptom management during cancer treatment. She is a member of the American Society of Clinical Oncology and the Society for Integrative Oncology, and a co-author on the Society for Integrative Oncology and ASCO guideline for integrative management of anxiety and depression in adults with cancer. This podcast is intended for educational and informational purposes only and should not be considered medical advice. Always consult a qualified healthcare professional regarding diagnosis, treatment, or medical decisions.