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.

Two of the most widely used chemotherapy drugs in the world, 5-FU and capecitabine, have been in use since the 1950s. A small share of patients carry variants in a gene called DPYD that slow their ability to break these drugs down, which means a standard dose behaves like an overdose in their body.

A single genetic test can identify those patients before the first treatment. Europe recommended universal screening in 2020. The FDA updated the labels for both drugs in 2025, after years of pressure from families who had lost someone.In this episode of Patient From Hell, host Samira Daswani speaks with Dr. Gabe Brooks, a medical oncologist at the Dartmouth Cancer Center, about what DPD deficiency is, what severe toxicity actually looks like, how and when to get screened, what the test costs, and the exact question to ask before starting either drug.

Guest:

Gabriel Brooks, MD, MPH, is a medical oncologist and Associate Professor of Medicine at the Dartmouth Cancer Center and the Geisel School of Medicine. He co-directs the Cancer Population Sciences Research Program and specializes in gastrointestinal cancers, including colorectal cancer.

Chapters

00:00 Introduction

00:27 What DPYD is and why it matters

02:50 When toxicity turns fatal

04:21 5-FU vs. capecitabine

06:16 Which cancers use these drugs

06:53 What the FDA changed

08:26 Why the U.S. took five years longer than Europe

11:27 Warning signs and time to onset

15:28 How and when to get screened

17:39 Germline DNA vs. tumor genomic testing

20:16 The patient advocacy behind the change

24:44 What to ask your oncologist

26:43 What the test costs

28:18 Closing thoughts

Resources:

Advocates for Universal DPD/DPYD Testing — test4dpd.org🎙️

Patient From Hell is hosted by Samira Daswani, cancer survivor, entrepreneur, and founder of Manta Cares. Through candid conversations with patients, physicians, researchers, and healthcare leaders, the show explores the realities of cancer care while empowering patients with practical, evidence-based information.

🔗 Connect with Patient From Hell

Website: https://www.mantacares.com

Disclaimer

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.

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.Recorded on location at the San Antonio Breast Cancer Symposium, December 2025.Metastatic triple-negative breast cancer remains the breast cancer subtype with the fewest targetable biomarkers and the shortest treatment algorithm. When a trial reports a double-digit progression-free survival in the first-line setting, it is worth understanding what that actually changes and how the trial was designed with patient outcomes at the center.This episode was recorded in December 2025, before regulatory action. On June 24, 2026, the FDA approved sacituzumab govitecan-hziy for two first-line indications in triple-negative breast cancer: as a single agent for adults with unresectable locally advanced or metastatic TNBC who are not candidates for PD-1 or PD-L1 inhibitor-based therapy supported by ASCENT-0, and in combination with pembrolizumab for adults whose tumors express PD-L1 with a CPS of 10 or greater supported by ASCENT-04. Janice's speculation in this episode about how PD-L1 status might factor into the guidelines has since been answered by the label.ASCENT-04/KEYNOTE-D19 NCT05382286 was a phase 3, open-label, randomized trial of 443 patients with previously untreated locally advanced unresectable or metastatic TNBC whose tumors expressed PD-L1 at a CPS of 10 or greater by the 22C3 assay. Participants were randomized 1:1 to sacituzumab govitecan plus pembrolizumab or to physician's choice of chemotherapy plus pembrolizumab. Patients in the control arm with centrally confirmed progression were offered crossover to sacituzumab govitecan.0:00 Live from the San Antonio Breast Cancer Symposium0:30 The METAvivor ribbon and what the pink ribbon leaves out1:35 Diagnosed in 2016 with a median overall survival of 9 to 15 months2:26 Nine years later3:20 From pediatric nursing to research advocacy4:30 What has changed since 2017, and what has not5:26 2011: when chemotherapy was the only option5:55 On not knowing a relevant clinical trial existed6:47 Why metastatic TNBC still has no maintenance therapy7:25 What first-line treatment looks like today8:25 Inside ASCENT-049:09 Progression-free survival, defined9:59 Why a double-digit PFS is notable in this subtype11:20 Why each subsequent line of treatment works for less time11:52 How many patients never reach second line12:50 The case for a stronger first-line option13:21 Crossover design, and why it matters to patients14:33 What crossover means in a randomized trial15:56 Patient advocates in clinical trial design18:59 Quality of life versus quantity of life21:48 Rapid fire: metastatic breast cancer and metastatic TNBC23:06 Rapid fire: first line, second line, progression-free survival24:00 Rapid fire: immunotherapy and antibody-drug conjugates24:59 Advice for the newly diagnosed26:04 What she wants next: a biomarker26:52 On ADCs, tolerability, and the need for novel targetsJanice Cowden, RN is a research patient advocate living with metastatic triple-negative breast cancer. She practiced as a registered nurse for approximately 22 years, primarily in pediatrics, and later worked as a pharmaceutical sales representative. She was diagnosed with stage I triple-negative breast cancer in 2011 and with metastatic disease in 2016, and completed the Living Beyond Breast Cancer advocacy training program in 2017.This podcast is intended for educational and informational purposes only and should not be considered medical advice.