• K Kalinsky, J R Diamond, L T Vahdat, S M Tolaney, D Juric, J O'Shaughnessy, R L Moroose, I A Mayer, V G Abramson, D M Goldenberg, R M Sharkey, P Maliakal, Q Hong, T Goswami, W A Wegener, and A Bardia.
• Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center-Herbert Irving Comprehensive Cancer Center, New York, USA. Electronic address: kk2693@cumc.columbia.edu.
• Ann. Oncol. 2020 Dec 1; 31 (12): 1709-1718.

BackgroundTrophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody-drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020.Patients And MethodsWe analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) HR+/HER2- mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety.ResultsFifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%-45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7-12.7), median PFS was 5.5 months (95% CI 3.6-7.6), and median OS was 12 months (95% CI 9.0-18.2).ConclusionsSG shows encouraging activity in patients with pretreated HR+/HER2- mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339).Trial RegistrationClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552.Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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