Sacituzumab govitecan as second-line treatment for metastatic triple-negative breast cancer—phase 3 ASCENT study subanalysis

Abstract

Patients with triple-negative breast cancer (TNBC) who relapse early after (neo)adjuvant chemotherapy have more aggressive disease. In the ASCENT trial, sacituzumab govitecan (SG), an antibody-drug conjugate composed of an anti-Trop–2 antibody coupled to SN-38 via a hydrolyzable linker, improved outcomes over single-agent chemotherapy of physician’s choice (TPC) in metastatic TNBC (mTNBC). Of 468 patients without known baseline brain metastases, 33/235 vs 32/233 patients (both 14%) in the SG vs TPC arms, respectively, received one line of therapy in the metastatic setting and experienced disease recurrence ≤12 months after (neo)adjuvant chemotherapy. SG prolonged progression-free survival (median 5.7 vs 1.5 months [HR, 0.41; 95% CI, 0.22–0.76]) and overall survival (median 10.9 vs 4.9 months [HR, 0.51; 95% CI, 0.28–0.91]) vs TPC, with a manageable safety profile in this subgroup consistent with the overall population. In this second-line setting, as with later-line therapy, SG improved survival over conventional chemotherapy for patients with mTNBC.

Recent advances in therapeutic strategies for triple-negative breast cancer

“…PFS and OS were longer in the sacituzumab govitecan-treated group compared with physician’s choice (eribulin, vinorelbine, gemcitabine, or capecitabine). The mean PFS was 5.7 (2.6–8.1) vs. 1.5 (1.4–2.6) months in the two groups; the mean OS was 10.9 (6.9–19.5) vs. 4.9 (3.1–7.1) months, respectively [ 156 ].…”

Addiction of Cancer Stem Cells to MUC1-C in Triple-Negative Breast Cancer Progression

“…Sacituzumab govitecan (SG; IMMU-1320) is an ADC that targets TROP-2 for the selective delivery of the irinotecan metabolite SN-38 [ 44 ]. SG is the first ADC approved for the treatment of TNBC based on activity in the advanced-disease setting [ 45 , 46 , 47 , 48 ]. In contrast to MMAE, which targets microtubules with cell cycle arrest, SN-38 is a topoisomerase I inhibitor that induces DNA damage [ 44 ].…”

Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer

“…The longer median PFS, longer median overall survival, and higher ORR achieved with SG were compelling and clinically meaningful, especially in a population of patients who received a median of four prior anticancer regimens. This improvement in efficacy with SG was also observed in a subgroup analysis of patients who relapsed within 12 months of (neo)adjuvant therapy (10); this was notable because patients with early relapses (≤12 months) are likely to have more aggressive disease (11). A subgroup analysis of 61 patients with brain metastases was also conducted (12).…”