1. Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial
- Author
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William A. Wegener, David M. Goldenberg, RL Moroose, Joyce O'Shaughnessy, Dejan Juric, Aditya Bardia, Sara M. Tolaney, Jennifer R. Diamond, Vandana G. Abramson, Ingrid A. Mayer, Pius Maliakal, Linda T. Vahdat, T. Goswami, Kevin Kalinsky, Robert M. Sharkey, and Q. Hong
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Immunoconjugates ,Receptor, ErbB-2 ,Anemia ,medicine.medical_treatment ,Breast Neoplasms ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Microenvironment ,Humans ,Medicine ,Adverse effect ,Chemotherapy ,business.industry ,Hematology ,medicine.disease ,Metastatic breast cancer ,Hormones ,Confidence interval ,030104 developmental biology ,Oncology ,Hormone receptor ,030220 oncology & carcinogenesis ,Sacituzumab govitecan ,Camptothecin ,Female ,business - Abstract
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®) 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+/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. Results Fifty-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). Conclusions SG 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 registration ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552
- Published
- 2020
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