Journal
ANNALS OF ONCOLOGY
Volume 31, Issue 12, Pages 1709-1718Publisher
ELSEVIER
DOI: 10.1016/j.annonc.2020.09.004
Keywords
antibody-drug conjugate; SN-38; Trop-2; IMMU-132-01; TROPiCS-02
Categories
Funding
- Immunomedics, Inc.
- National Institutes of Health [CA39841]
- American Cancer Society
- NJ Commission on Cancer Research
- Garden State Cancer Research Foundation
- Escalon Foundation
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Background: Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor -positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy (R)) 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 methods: We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) HR+/HER2mBC 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. Results: Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (3379) 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). Conclusions: SG shows encouraging activity in patients with pretreated HR+/HER2mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339).
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