Subgroup analyses from the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer

Abstract

In this post hoc analysis of the ASCENT study, we compared outcomes with sacituzumab govitecan (SG) vs single-agent chemotherapy in clinically important subgroups of patients with metastatic triple-negative breast cancer (mTNBC). Patients with mTNBC refractory to/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG or treatment of physician's choice (TPC) until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) per RECIST 1.1 by central review in patients without brain metastases. Patients with brain metastases were allowed if metastases were stable ≥4 weeks. In the intention-to-treat (ITT) population, 19% of patients were age ≥65 years; 12% were Black, and 12% had brain metastases. SG improved PFS and overall survival (OS), respectively, vs TPC in patients age ≥65 years (7.1 vs 2.4 months and 14.7 vs 8.9 months), or of Black race (5.4 vs 2.2 months and 13.8 vs 8.5 months), consistent with outcomes in the ITT population. Patients with brain metastases had numerically higher median PFS with SG vs TPC, but median OS was similar between treatment groups. SG was well tolerated and had a manageable safety profile consistent with the full safety population across all subgroups; neutropenia and diarrhea were the most common treatment-emergent adverse events. These findings confirm the meaningful clinical benefit of SG vs standard chemotherapy in patient subgroups with high unmet needs. SG should be considered an effective and safe treatment option for patients with mTNBC eligible for second-line or later therapy. ClinicalTrials.gov Number: NCT02574455.

Fig. 1. CONSORT diagram.

^aPatients in the TPC arms were randomized to eribulin (n = 139), vinorelbine (n = 52), gemcitabine (n = 38), or capecitabine (n = 33). Details of the trial profile for the BMNeg population have been published previously. Reasons the patients discontinued treatment in each subgroup are presented in Table S1 in the Supplemental Appendix. Other race subgroup includes any patient who did not self-identify as Black race. BMNeg brain metastases-negative, BMPos brain metastases-positive, ITT intention to treat, SG sacituzumab govitecan, TPC treatment of physician’s choice.

Fig. 2. Subgroup analysis of progression-free survival and overall survival.

a Progression-free survival; b overall survival. Survival outcomes were assessed in the intention-to-treat population (all randomly assigned patients with and without brain metastases). Other race subgroup includes any patient who did not self-identify as Black race. PFS was determined by blinded independent central review according to Response Evaluation Criteria in Solid Tumors, version 1.1. OS overall survival, PFS progression-free survival, SG sacituzumab govitecan, TPC treatment of physician’s choice.