According to the phase 2 SACI-IO HR+ trial, the addition of pembrolizumab to sacituzumab govitecan showed a non-significant trend toward improvement in progression-free survival (PFS) among unselected patients with HR-positive, HER2-negative metastatic breast cancer.

These data were presented by Ana Garrido-Castro, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

The analysis of this randomized, open-label trial included 104 patients with unresected locally advanced or metastatic HR-positive, HER2-negative breast cancer treated with ≥1 prior endocrine therapy and ≤1 chemotherapy for metastatic breast cancer. Patients were randomized on a 1-to-1 basis to receive either sacituzumab govitecan plus pembrolizumab (combination arm, n = 52) or sacituzumab govitecan alone (monotherapy arm, n = 52). The primary end point was progression-free survival (PFS) with secondary end points including PFS among PD-L1-positive patients, overall survival (OS), objective response rate (ORR), and toxicity.

Dr Garrido-Castro stated at the presentation, “The addition of pembrolizumab to [sacituzumab govitecan] did not significantly improve median progression-free survival compared to [sacituzumab govitecan] alone in the intent-to-treat population.” She went on, “At a median follow-up of 12.5 months, there was no significant difference in median overall survival observed between the treatment arms.” With a median follow-up duration of 9.2 months, the median PFS was 8.1 months in the combination arm vs 6.2 months in the monotherapy arm (hazard ratio [HR], 0.81; P = 0.37). The median OS was 18.52 months in the combination arm vs 17.96 months in the monotherapy arm (HR, 0.65; P = 0.21). Dr Garrido-Castro added, among patients with PD-L1-positive disease, defined as CPS ≥1, “a non-significant 4.4 month increase in median PFS and 6-month increase in median OS were observed favoring the combination.”

The most frequent grade ≥2 treatment-related toxicities in the combination arm were neutropenia, fatigue, alopecia, anemia, leukopenia, diarrhea, and nausea. The most frequent grade ≥2 treatment-related toxicities in the monotherapy arm were neutropenia, alopecia, diarrhea, nausea, fatigue, and anemia.

Dr Garrido-Castro concluded, “We think that these results support further investigation of [sacituzumab govitecan] plus pembrolizumab in patients with PD-L1-positive, HR-positive, HER2-negative, metastatic breast cancer. Additional work is needed to investigate predictors of benefit from [antibody drug conjugates] and immune checkpoint inhibitor combination strategies in HR-positive, HER2-negative metastatic breast cancer.”

Source:

Garrido-Castro AC, Kim SE, Desrosiers J, et al. SACI-IO HR+: A randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer. Presented at the ASCO Annual Meeting. May 31 – June 4, 2024; Chicago, IL. Abstract #LBA1004