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For patients diagnosed with metastatic triple-negative breast cancer (TNBC), treatment options have changed dramatically in recent years, but there is still a major unmet need.
In this episode of The Patient From Hell, Samira Daswani sits down with Dr. Sara M. Tolaney, MD, MPH, FASCO, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School, to break down one of the most important recent developments in metastatic TNBC: the ASCENT-04/KEYNOTE-D19 trial.
The conversation explores what the ASCENT-04 results mean for patients, how antibody-drug conjugates (ADCs) work, why PD-L1 testing matters, and how the treatment landscape is rapidly evolving for people with metastatic triple-negative breast cancer.
At the 2025 ASCO Annual Meeting, Dr. Tolaney presented the primary results of ASCENT-04, a randomized Phase 3 trial comparing sacituzumab govitecan plus pembrolizumab with chemotherapy plus pembrolizumab in previously untreated patients with PD-L1-positive advanced TNBC. The trial showed a significant improvement in progression-free survival, from 7.8 months to 11.2 months.
Since the episode was recorded, the findings have translated into clinical practice: on June 24, 2026, the FDA approved sacituzumab govitecan-hziy (Trodelvy) with pembrolizumab for the first-line treatment of adults with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (CPS ≥10).
Episode Highlights
- What ASCENT-04/KEYNOTE-D19 found: Sacituzumab govitecan plus pembrolizumab produced a median progression-free survival of 11.2 months versus 7.8 months with chemotherapy plus pembrolizumab.
- Why antibody-drug conjugates are different: Dr. Tolaney explains ADCs as a targeted delivery system that uses an antibody to identify cancer cells and deliver chemotherapy directly into them.
- Why PD-L1 testing matters: For metastatic TNBC, PD-L1 status can influence whether a patient is eligible for immunotherapy and can now help determine first-line treatment options.
- What “controlling” metastatic cancer means: Rather than automatically framing metastatic breast cancer around cure, the goal is often to keep disease stable or shrinking for as long as possible while maintaining quality of life.
- Why genomic testing matters: Germline BRCA testing, tumor sequencing, and other biomarkers can reveal additional treatment options or clinical-trial opportunities.
- Why clinical trials matter: With new antibody-drug conjugates, targeted therapies, immunotherapies, and other approaches rapidly entering the field, patients may benefit from treatment at an academic or specialized cancer center with access to clinical trials.
About Dr. Sara M. Tolaney
Sara M. Tolaney, MD, MPH, FASCO, is a breast medical oncologist and clinical investigator at Dana-Farber Cancer Institute. She serves as Chief of the Division of Breast Oncology and Associate Director of the Susan F. Smith Center for Women’s Cancers, and is an Associate Professor of Medicine at Harvard Medical School. Her clinical and research interests include breast oncology, immuno-oncology, and novel therapeutics.
Dr. Tolaney has played a significant role in developing and studying new breast cancer treatments, including antibody-drug conjugates, immunotherapy, and targeted approaches. She serves on the National Cancer Institute Breast Cancer Steering Committee and is Vice Chair for Late-Stage Development in Breast Cancer in the Alliance for Clinical Trials in Oncology. She has also chaired and led multiple Phase 3 breast cancer trials.
Her work on ASCENT-04 placed her at the center of one of the major metastatic TNBC data presentations at the 2025 ASCO Annual Meeting, where the Phase 3 study results were presented as an oral abstract.
Pull Quote
“There are a lot of treatment choices, and it is continuously evolving.”
For patients facing metastatic triple-negative breast cancer, Dr. Tolaney emphasizes that the treatment landscape is changing so quickly that information from even one year ago may no longer fully reflect today's options. She encourages patients to understand their treatment choices and ask about clinical trials.
What ASCENT-04 Means for Patients
ASCENT-04 evaluated 443 patients with previously untreated advanced or metastatic TNBC whose tumors expressed PD-L1. Patients were randomly assigned to sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab. The combination with sacituzumab produced a median progression-free survival of 11.2 months compared with 7.8 months for chemotherapy plus pembrolizumab.
The study also showed a longer median duration of response: 16.5 months versus 9.2 months. Overall survival data were still immature in the initial analysis.
The significance extends beyond one clinical trial. The episode explains how the field is increasingly moving antibody-drug conjugates and other targeted therapies earlier in the treatment journey instead of reserving them for later lines of therapy.
That shift is particularly important because, as Dr. Tolaney explains, some patients with metastatic TNBC may deteriorate or die before ever reaching a second-line treatment. Moving effective therapies into first-line treatment could therefore make a meaningful difference.
What Happens After Diagnosis?
Dr. Tolaney explains that treatment decisions for metastatic breast cancer increasingly depend on understanding the biology of an individual's cancer.
Testing can include:
Estrogen receptor, progesterone receptor, and HER2: These help establish whether a cancer is triple-negative.
PD-L1: In metastatic TNBC, PD-L1 status can help determine whether an immunotherapy-containing regimen is appropriate.
Germline BRCA testing: An inherited BRCA1 or BRCA2 mutation may open the door to PARP inhibitor treatment.
Tumor genomic sequencing: Sequencing can identify somatic mutations and other alterations that may inform later treatment decisions or clinical-trial eligibility.
This is part of the larger shift toward increasingly personalized cancer treatment—where the question is no longer simply “What treatment do people with this cancer usually receive?” but “What does this specific cancer tell us about the treatment options available to this patient?”
The Bigger Picture: A Rapidly Changing TNBC Landscape
Dr. Tolaney has watched the treatment landscape change from an era when chemotherapy was essentially the main systemic option for triple-negative breast cancer to one featuring antibody-drug conjugates, immunotherapy, PARP inhibitors, targeted therapies, and an expanding pipeline of clinical trials.
As she puts it, the pace of change means that what was true about metastatic TNBC treatment a year ago may no longer be the full picture today.
And that evolution continued after the recording of this episode.
In June 2026, the FDA approved sacituzumab govitecan-hziy with pembrolizumab for first-line treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC, based on ASCENT-04/KEYNOTE-D19. The FDA reported median progression-free survival of 11.2 months versus 7.8 months, with confirmed objective response rates of 61% and 55%, respectively.
New analyses presented at ASCO 2026 also examined benefit beyond the initial progression-free survival endpoint, with progression-free survival after next-line treatment favoring sacituzumab govitecan plus pembrolizumab despite crossover between treatment groups.
For patients and families, the takeaway is not that one drug has solved metastatic TNBC. It is that the menu of options continues to grow—and understanding the biology of the cancer and access to experienced breast oncology teams can matter enormously.
Resources
- Dana-Farber Cancer Institute — Sara M. Tolaney, MD, MPH: https://www.dana-farber.org/find-a-doctor/sara-m-tolaney
- ASCENT-04/KEYNOTE-D19 — ASCO: Primary trial results and presentation information.
- FDA — Sacituzumab Govitecan + Pembrolizumab: Current first-line TNBC approval information.
- ClinicalTrials.gov: ASCENT-04/KEYNOTE-D19, NCT05382286.
- 2025 ASCO Annual Meeting: Primary ASCENT-04 results were presented by Dr. Tolaney as an oral abstract.
Tags
metastatic triple negative breast cancer, triple negative breast cancer treatment, ASCENT-04, ASCENT-04 KEYNOTE-D19, Dr. Sara Tolaney, Dana-Farber Cancer Institute, antibody drug conjugates, sacituzumab govitecan, pembrolizumab, PD-L1 breast cancer, breast cancer immunotherapy, metastatic breast cancer, cancer clinical trials
