Sacituzumab govitecan plus pembrolizumab falls short of prolonging PFS in metastatic breast cancer

Combination treatment with sacituzumab govitecan (SG) and pembrolizumab does not improve outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) unselected by programmed death-ligand 1 (PD-L1), as shown in a phase II trial.

Patients with HR-positive/HER2-negative MBC pretreated with endocrine therapy and 0‒1 chemotherapy regimen for MBC were randomized to receive SG plus pembrolizumab or SG alone.

Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included PFS in the PD-L1-positive population, overall survival (OS), objective response rate (ORR), and toxicity. The investigators collected baseline tumour tissue and plasma samples for correlative analyses.

Some 104 patients began receiving treatment between March 2021 and January 2024, of whom 49 (47 percent) had not received chemotherapy for MBC.

At a median follow-up of 15.5 months, SG plus pembrolizumab failed to significantly improve PFS compared with SG alone (8.4 vs 6.7 months; hazard ratio [HR], 0.76, 95 percent confidence interval [CI], 0.48‒1.19; p=0.12). Results were also similar for the median OS (20.0 vs 18.0 months; p=0.18) and ORR (28.8 percent vs 19.2 percent; p=0.36).

In the PD-L1-positive population (44 percent; 39/88 with tissue), the median PFS (11.1 vs 5.6 months; HR, 0.51, 95 percent CI, 0.24‒1.12; p=0.09) and OS (18.5 vs 12.5 months; HR, 0.59, 95 percent CI, 0.18‒1.98; p=0.39) were numerically higher with the combination treatment.

The most common grade ≥2 adverse events were neutropenia, alopecia, fatigue, anaemia, nausea, leukopenia, and diarrhoea.

“In the PD-L1-positive population, the trend in PFS and OS favouring SG plus pembrolizumab warrants further investigation in larger randomized trials,” the investigators said.

SG is a TROP2-directed topoisomerase I-inhibitor antibody–drug conjugate approved for chemorefractory HR-positive/HER2-negative MBC.