In patients with metastatic hormone receptor (HR)-positive/HER2-negative breast cancer unselected by PD-L1 status, adding the immune checkpoint inhibitor pembrolizumab to the antibody-drug conjugate sacituzumab govitecan-hziy resulted in a 1.9-month improvement in median progression-free survival that was not statistically significant. In a subgroup of patients with PD-L1–positive tumors (defined as having a combined positive score of ≥ 1), a 4.4-month increase in median progression-free survival was observed with sacituzumab govitecan plus pembrolizumab compared to sacituzumab govitecan alone. These results were presented by Ana Christina Garrido-Castro, MD, and colleagues at the 2024 ASCO Annual Meeting (Abstract LBA1004).
SACI-IO HR+
The phase II SACI-IO HR+ trial was designed to evaluate whether these two therapies acted synergistically. Sacituzumab govitecan consists of a TROP-2–directed antibody linked to a chemotherapy drug called SN-38. In cancer cells, SN-38 causes DNA damage that, via activation of pathways in the cancer cell, may draw T cells to the cancer. Combining the agent with pembrolizumab could enhance the ability of the immune system to recognize and attack cancer cells, researchers hypothesized. The SACI-IO HR+ trial included 110 previously treated patients with advanced or metastatic HR-positive/HER2-negative breast cancer; 104 patients started therapy on the study—half of whom received sacituzumab govitecan plus pembrolizumab and half of whom received sacituzumab govitecan alone.
At a median follow-up of 12.5 months, the median progression-free survival was 8.1 months for patients receiving the combination therapy compared to 6.2 months for those receiving sacituzumab govitecan alone. In the approximately 40% of patients who participated in the study whose tumor was PD-L1–positive, the median progression-free survival was 11.1 months with the combination vs 6.7 months with sacituzumab govitecan alone.
These results support further investigation of sacituzumab govitecan plus pembrolizumab in patients with PD-L1–positive metastatic HR-positive/HER2-negative breast cancer.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
