Sacituzumab govitecan: a new opportunity in the treatment of refractory metastatic triple-negative breast cancer

Abstract

Bardia and colleagues performed a phase 3 trial to evaluate sacituzumab govitecan (SG) [an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell surface antigen 2 (Trop-2)], compared to single agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine or gemcitabine) in patients with relapsed or refractory metastatic triple negative breast cancer (mTNBC) (1). The primary endopoint was progression free survival (PFS) in 468 patients without known baseline brain metastasis. All were previously treated with taxanes. The secondary endpoints were overall survival (OS), PFS (investigator assessment), objective response rate (ORR) and safety. The authors reported that patients with mTNBC pretreated with at least two lines of treatment had a significant superiority of SG over chemotherapy in terms of survival and a tolerable safety profile, with a median progression-free survival of 5.6 vs. 1.7 months, and an OS of 12.1 vs. 6.7 months, respectively (1). SG had an OR of 35% in the arm of SG and 5% in the arm of chemotherapy. The median PFS was 4.8 months with SG and 1.7 months with standard chemotherapy. The median OS was 11.8 months with SG and 6.9 months with chemotherapy. Clinical benefit was obtained in all the subgroups of patients evaluated and was independent from the level of Trop 2 expression as reported in the biomarker analysis of ASCENT study by Bardia et al. (2). In particular, the median relative dose intensity with SG was 99.7%. The most frequent adverse events related to SG treatment were neutropenia (63% with SG and 43% with chemotherapy), diarrhea (59% with SG and 12% with chemotherapy), nausea (57% with SG and 26% with chemotherapy), alopecia (46% with SG vs. 16% with chemotherapy), fatigue (45% with SG vs. 30% with chemotherapy), anemia (34% with SG vs. 24% with chemotherapy). Despite diarrhea and myelosuppression were the primary adverse events, the discontinuation rates were very low (5% in each group). The most frequent treatment-related adverse events of grade 3 (severe, according to Common Terminology Criteria for Adverse Events, CTCAE) or higher were neutropenia (51% with SG and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). In particular neutropenia was managed with dose reduction, dose delay, or both and with growth-factor support after day 1 of cycle 1. The incidence of grade 3 and 4 febrile neutropenia was 5% and 1% respectively, with SG and 2% and less than 1%, respectively, with chemotherapy. In addition, at the same time, growth-factor support was given to 49% of the patients treated with SG and 23% of patients treated with chemotherapy. The results of this study have changed clinical practice of patients with mTNBC from the second line of treatment and beyond. SG, a first-in-class Trop-2-directed antibody-drug conjugate, demonstrated a significant benefit with respect to progression-free and OS in comparison with standard-Editorial Commentary