Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer

Purpose Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38 via a proprietary hydrolyzable linker. In the ASCENT study, SG improved survival versus single-agent treatment of physician's choice (TPC) in pre-treated metastatic triple-negative breast cancer (mTNBC). Hormone/HER2 receptor changes are common, particularly at relapse/metastasis. This subanalysis assessed outcomes in patients who did/did not have TNBC at initial diagnosis, before enrollment. Methods TNBC diagnosis was only required at study entry. Patients with mTNBC refractory/relapsing after >= 2 prior chemotherapies were randomized 1:1 to receive SG or TPC. Primary endpoint was progression-free survival (PFS) in patients without brain metastases. Results Overall, 70/235 (30%) and 76/233 (33%) patients who received SG and TPC, respectively, did not have TNBC at initial diagnosis. Clinical benefit with SG versus TPC was observed in this subset. Median PFS was 4.6 versus 2.3 months (HR 0.48; 95% CI 0.32-0.72), median overall survival was 12.4 versus 6.7 months (HR 0.44; 95% CI 0.30-0.64), and objective response rate (ORR) was 31% versus 4%; those who also received prior CDK4/6 inhibitors had ORRs of 21% versus 5%. Efficacy and safety for patients with TNBC at initial diagnosis were generally similar to those who did not present with TNBC at initial diagnosis. Conclusion Patients without TNBC at initial diagnosis had improved clinical outcomes and a manageable safety profile with SG, supporting SG as a treatment option for mTNBC regardless of subtype at initial diagnosis. Subtype reassessment in advanced breast cancer allows for optimal treatment. Clinical trial registration number NCT02574455, registered October 12, 2015.

Automated summary

This study analyzed the efficacy of sacituzumab govitecan in patients with metastatic triple-negative breast cancer (mTNBC). The results showed that regardless of whether patients had TNBC at initial diagnosis, sacituzumab govitecan improved clinical outcomes. For patients without TNBC at initial diagnosis, the clinical efficacy and safety of sacituzumab govitecan were manageable.