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 resulted in a 1.9-month improvement in median progression-free survival that was not statistically significant.

The research teams presented their findings at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, May 31-June 4, 2024.

In the subgroup of patients with PD-L1-positive tumours (defined as a combined positive score ≥1), a 4.4-month increase in median progression-free survival was observed with sacituzumab govitecan plus pembrolizumab compared to sacituzumab govitecan alone.

The phase II SACI-IO HR+ trial was designed to evaluate whether these two therapies act synergistically. Sacituzumab govitecan consists of an 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.

The combination with pembrolizumab (an immune checkpoint inhibitor that lifts the brakes off the immune system) could enhance the ability of the immune system to recognise and attack cancer cells.

The SACI-IO HR+ trial included 110 patients with previously treated 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 (how long patients lived before their cancer worsened) was 8.1 months for patients receiving the combined 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.

Source: Dana-Farber Cancer Institute