Sara M. Tolaney, MD, MPH, FASCO, on PD-L1–Positive Advanced TNBC: First-Line Doublet Comparison
2025 ASCO Annual Meeting
Sara M. Tolaney, MD, MPH, FASCO, of Dana-Farber Cancer Institute and Harvard Medical School, discusses findings from the phase III ASCENT-04/KEYNOTE-D19 study, which compared sacituzumab govitecan-hziy plus pembrolizumab vs chemotherapy plus pembrolizumab in previously untreated patients with PD-L1–positive advanced triple-negative breast cancer (TNBC) (LBA109).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
At ASCO this year, we presented results from the ASCENT-04 trial. This is a randomized phase three study of sacituzumab govitecan plus pembrolizumab compared to chemotherapy plus pembrolizumab in patients who have previously untreated PD-L1–positive metastatic triple-negative breast cancer. We know that about 15% of all breast cancers are triple-negative, and about 40% of triple-negative breast cancers are PD-L1–positive. Currently, these patients are treated with chemotherapy and checkpoint inhibition, where we've seen median progression-free survival that ranges between 7 to 9 months. We also have antibody-drug conjugates to treat pretreated metastatic triple-negative disease, and sacituzumab govitecan is a Trop-2–directed antibody-drug conjugate that has previously been found to improve both progression-free and overall survival in pretreated metastatic triple-negative breast cancer and is currently a second-line standard-of-care option. There has been a lot of interest in combining antibody-drug conjugates with checkpoint inhibitors given some robust preclinical and clinical data. And so ASCENT-04 was really designed to test the efficacy of sacituzumab plus pembrolizumab. This trial was designed in patients who had no prior systemic therapy in the metastatic triple-negative setting. They had to either have de novo metastatic disease or be at least six months out from completion of any systemic therapy in the early disease setting. Prior use of checkpoint inhibition for early-stage breast cancer was allowed, and patients were randomized 1:1 to receive sacituzumab govitecan plus pembrolizumab or chemotherapy. A physician’s choice plus pembrolizumab or choice of chemotherapy could either be paclitaxel, nab-paclitaxel, or carboplatin and gemcitabine. For those patients on the chemotherapy plus pembrolizumab arm, if they progressed, they were allowed to get crossover treatment with sacituzumab govitecan monotherapy if they had centrally confirmed disease progression during the crossover phase of the study. The primary endpoint was progression-free survival by blinded independent central review, and the primary endpoint progression-free survival data demonstrated that sacituzumab plus pembrolizumab led to significant improvement in progression-free survival when compared to chemotherapy plus pembrolizumab, with an improvement in PFS going from 7.8 to 11.2 months with a hazard ratio of 0.65 and an absolute difference of about 3.4 months. Seeing these data with an improvement in PFS suggests that the combination of sacituzumab and pembrolizumab could represent a new standard-of-care option for patients who have previously untreated PD-L1–positive metastatic triple-negative breast cancer.
The ASCO Post Staff
Yelena Y. Janjigian, MD, of Memorial Sloan Kettering Cancer Center, presents event-free survival data from the phase III MATTERHORN trial of the PD-L1 inhibitor durvalumab plus FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy) in patients with resectable gastric or gastroesophageal junction (GEJ) cancer (LBA5).
The ASCO Post Staff
Hope S. Rugo, MD, FASCO, of City of Hope, and Rebecca Alexandra Dent, MD, FASCO, of National Cancer Centre Singapore, review the results of a biomarker analysis of the DESTINY-Breast06 trial, which evaluated trastuzumab deruxtecan after endocrine therapy in patients with metastatic breast cancer (Abstract 1013). They also discuss findings from the SERENA-6 and EMBER-3 trials, also presented at ASCO 2025, and what all this new data means for the sequencing of endocrine therapy in patients with breast cancer.
The ASCO Post Staff
Bjorn Henning Gronberg, MD, PhD, of Norwegian University of Science and Technology (NTNU) and St. Olavs Hospital, presents phase II findings on the efficacy of atezolizumab after chemoradiotherapy (CRT) in limited-stage small cell lung cancer (SCLC) (LBA8005).
The ASCO Post Staff
Andrew Kuykendall, MD, of Moffitt Cancer Center, discusses findings from the phase III VERIFY trial, which compared the efficacy of rusfertide vs placebo in patients with polycythemia vera who continue their current standard of care therapy (Abstract LBA3).
The ASCO Post Staff
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, reviews the final analysis of phase II CAPTIVATE study demonstrating the long-term efficacy and safety of ibrutinib plus venetoclax for previously untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including in patients with high-risk genomic features. The 5.5-year progression-free survival and overall survival rates were 66% and 97%, respectively (Abstract 7036).