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J Clin Oncol. 2017 Jul 1;35(19):2141-2148. doi: 10.1200/JCO.2016.70.8297. Epub 2017 Mar 14.

Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer.

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Aditya Bardia, Steven J. Isakoff, and Dejan Juric, Massachusetts General Hospital Cancer Center; Aditya Bardia, Steven J. Isakoff, Dejan Juric, and Sara M. Tolaney, Harvard Medical School; Sara M. Tolaney, Dana-Farber Cancer Institute, Boston, MA; Ingrid A. Mayer, Vandana Abramson, and Jordan Berlin, Vanderbilt-Ingram Cancer Center, Nashville, TN; Jennifer R. Diamond and Wells A. Messersmith, University of Colorado Cancer Center, Aurora, CO; Rebecca L. Moroose and Nikita C. Shah, University of Florida Health Cancer Center, Orlando, FL; Alexander N. Starodub, Indiana University Health Center for Cancer Care, Goshen, IN; Joyce O'Shaughnessy, Texas Oncology-Baylor Charles A. Sammons Cancer Center; Joyce O'Shaughnessy, US Oncology, Dallas, TX; Kevin Kalinsky, Columbia University Herbert Irving Comprehensive Cancer Center; Allyson J. Ocean and Linda T. Vahdat, Weill Cornell Medicine, New York, NY; Michael Guarino, Helen F. Graham Cancer Center, Newark, DE; William A. Wegener, Pius Maliakal, Robert M. Sharkey, Serengulam V. Govindan, and David M. Goldenberg, Immunomedics, Morris Plains, NJ.


Purpose Trop-2, expressed in most triple-negative breast cancers (TNBCs), may be a potential target for antibody-drug conjugates. Sacituzumab govitecan, an antibody-drug conjugate, targets Trop-2 for the selective delivery of SN-38, the active metabolite of irinotecan. Patients and Methods We evaluated sacituzumab govitecan in a single-arm, multicenter trial in patients with relapsed/refractory metastatic TNBC who received a 10 mg/kg starting dose on days 1 and 8 of 21-day repeated cycles. The primary end points were safety and objective response rate; secondary end points were progression-free survival and overall survival. Results In 69 patients who received a median of five prior therapies (range, one to 12) since diagnosis, the confirmed objective response rate was 30% (partial response, n = 19; complete response, n = 2), the median response duration was 8.9 (95% CI, 6.1 to 11.3) months, and the clinical benefit rate (complete response + partial response + stable disease ≥ 6 months) was 46%. These responses occurred early, with a median onset of 1.9 months. Median progression-free survival was 6.0 (95% CI, 5.0 to 7.3) months, and median overall survival was 16.6 (95% CI, 11.1 to 20.6) months. Grade ≥ 3 adverse events included neutropenia (39%), leukopenia (16%), anemia (14%), and diarrhea (13%); the incidence of febrile neutropenia was 7%. The majority of archival tumor specimens (88%) were moderately to strongly positive for Trop-2 by immunohistochemistry. No neutralizing antibodies to the ADC or antibody were detected, despite repeated cycles developed. Conclusion Sacituzumab govitecan was well tolerated and induced early and durable responses in heavily pretreated patients with metastatic TNBC. As a therapeutic target and predictive biomarker, Trop-2 warrants further research.

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