Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer

Author(s): Sara M. Tolaney, M.D.¹; Evandro de Azambuja, M.D., Ph.D.²; Kevin Kalinsky, M.D.³; Sherene Loi, M.D., Ph.D.⁴; Sung-Bae Kim, M.D., Ph.D.⁵; Clinton Yam, M.D.⁶; Bernardo Rapoport, Dip. in Med., M.Med.^7,8; Seock-Ah Im, M.D., Ph.D.⁹; Barbara Pistilli, M.D.¹⁰; Wassim Mchayleh, M.D.¹¹; David W. Cescon, M.D., Ph.D.¹²; Junichiro Watanabe, M.D., Ph.D.¹³; Manuel Alejandro Lara Bañuelas, M.D.¹⁴; Ruffo Freitas-Junior, M.D., Ph.D.¹⁵; Javier Salvador Bofill, M.D., Ph.D.¹⁶; Maryam Afshari, Pharm.D.¹⁷; Dianna Gary, B.S.N.¹⁷; Lu Wang, M.S.¹⁷; Catherine Lai, Pharm.D.¹⁷; Peter Schmid, M.D., Ph.D.¹⁸; the ASCENT-04/KEYNOTE-D19 Clinical Trial Investigators*;

Source: DOI: 10.1056/NEJMoa2508959

Dr. Anjan Patel's Thoughts

This really feels like a first-line practice changer in PD-L1+ MTNBC—the sacituzumab govitecan/pembrolizumab combination delivering a 3.4-month progression-free survival (PFS) improvement and pushing median PFS past 11 months is quite meaningful. Mature overall survival (OS) data will be interesting to see. Remember to watch closely and consider screening for drug-induced interstitial lung disease(ILD).

BACKGROUND

Triple-negative breast cancer is an aggressive breast cancer subtype, and there remains an unmet need to improve outcomes in patients with previously untreated, programmed death ligand 1 (PD-L1)–positive, locally advanced unresectable or metastatic triple-negative breast cancer.

METHODS

In this phase 3, open-label, international trial, we randomly assigned patients in a 1:1 ratio to receive sacituzumab govitecan plus pembrolizumab or chemotherapy plus pembrolizumab. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included overall survival, objective response (complete or partial response) and duration of response as assessed by blinded independent central review, and safety. Research Summary Sacituzumab Govitecan plus Pembrolizumab for Breast Cancer

RESULTS

A total of 443 patients were randomly assigned to receive sacituzumab govitecan plus pembrolizumab (221 patients) or chemotherapy plus pembrolizumab (222 patients). The median progression-free survival was 11.2 months (95% confidence interval [CI], 9.3 to 16.7) with sacituzumab govitecan plus pembrolizumab and 7.8 months (95% CI, 7.3 to 9.3) with chemotherapy plus pembrolizumab (hazard ratio for disease progression or death, 0.65; 95% CI, 0.51 to 0.84; two-sided P

CONCLUSIONS

Sacituzumab govitecan plus pembrolizumab led to significantly longer progression-free survival than chemotherapy plus pembrolizumab among patients with previously untreated, PD-L1–positive, advanced triple-negative breast cancer. (Funded by Gilead Sciences; ASCENT-04/KEYNOTE-D19 ClinicalTrials.gov number, NCT05382286.)

Author Affiliations

¹Dana–Farber Cancer Institute, Harvard Medical School, Boston; ²Institut Jules Bordet, Hôpital Universitaire de Bruxelles and Université Libre de Bruxelles, Brussels; ³Winship Cancer Institute, Emory University, Atlanta; ⁴Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; ⁵Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; ⁶University of Texas M.D. Anderson Cancer Center, Houston; ⁷Medical Oncology Centre of Rosebank, Clinical and Translational Research Unit, Saxonwold, South Africa; ⁸Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; ⁹Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea; ¹⁰Department of Cancer Medicine, Gustave Roussy, Villejuif, France; ¹¹AdventHealth Cancer Institute, Orlando, FL; ¹²Princess Margaret Cancer Centre, University Health Network, Toronto; ¹³Juntendo University Graduate School of Medicine, Tokyo; ¹⁴SCIENTIA Investigación Clínica, Chihuahua, Mexico; ¹⁵Araujo Jorge Cancer Hospital, Goias Anticancer Association, Goiânia, Brazil; ¹⁶Medical Oncology Department, Hospital Universitario Virgen del Rocio, Seville, Spain; ¹⁷Gilead Sciences, Foster City, CA; ¹⁸Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London

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