Antibody–Drug Conjugates Moving to the First-Line Setting in Triple-Negative Breast Cancer

Chemotherapy is the mainstay of treatment for patients with previously untreated metastatic triple-negative breast cancer (TNBC) who are not candidates for immunotherapy and concurrent chemotherapy. Might antibody–drug conjugates, which have been largely reserved for later lines of therapy, be effective in this setting?

In the ASCENT-03 trial, 560 patients with metastatic TNBC who had not previously received systemic therapy for advanced disease and were ineligible for checkpoint (PD-1 or PD-L1) inhibitor therapy were randomized to receive either sacituzumab govitecan or standard chemotherapy. Per exclusion criteria, none of the patients had disease recurrence within 6 months of completing curative therapy.

Key results were as follows:

• Patients receiving sacituzumab govitecan had significantly longer progression-free survival (PFS) than those receiving chemotherapy (median, 9.7 vs. 6.9 months).
• Objective response rates were similar between the groups (48% and 46%).
• Overall survival remains immature.
• In all subgroup analyses, sacituzumab govitecan was more beneficial than standard chemotherapy.
• No unexpected toxicities were reported. Adverse events of grade 3 or higher occurred in 66% of the sacituzumab govitecan group and 62% of the placebo group.