Dr Tolaney on Data With Checkpoint Inhibitor Combinations in Metastatic TNBC

Sara M. Tolaney, MD, MPH, chief, Division of Breast Oncology, associate director, Susan F. Smith Center for Women’s Cancers; senior physician, Dana-Farber Cancer Institute, associate professor, medicine, Harvard Medical School, discusses key data on checkpoint inhibitor combinations in metastatic triple-negative breast cancer (TNBC).

The phase 3 KEYNOTE-355 trial (NCT02819518) evaluated patients with metastatic TNBC who had not received prior therapy in the metastatic setting, Tolaney begins. In this study, patients were randomly assigned to receive either chemotherapy of the physician’s choice, which could be a taxane or carboplatin plus gemcitabine alone, or in combination with pembrolizumab, a checkpoint inhibitor, she reports. When the trial was initiated, it was not yet known that checkpoint inhibitors would primarily benefit patients with PD-L1–positive tumors, according to Tolaney. Therefore, the study was designed to include both PD-L1–positive and PD-L1–negative patient populations, Tolaney explains.

The results of the trial demonstrated significant improvements in both progression-free survival and overall survival for patients with PD-L1–positive tumors when treated with the combination of pembrolizumab and chemotherapy, she continues. Specifically, patients who met the criteria for PD-L1 positivity—defined by a combined positive score (CPS) of 10 or higher using the PD-L1 immunohistochemistry 22C3 assay—had marked benefits with the combination, she adds. Conversely, no significant improvements were observed in patients with PD-L1–negative tumors, indicating that the efficacy of pembrolizumab in combination with chemotherapy is closely tied to PD-L1 expression, Tolaney reports.

The findings from the KEYNOTE-355 trial underscore the importance of PD-L1 testing in metastatic TNBC, Tolaney explains. For patients with a CPS of 10 or higher, the addition of pembrolizumab to chemotherapy significantly improved both PFS and OS compared with chemotherapy alone, she reiterates. This finding has important implications for TNBC treatment strategies, highlighting the need for personalized treatment plans based on PD-L1 status, Tolaney adds.

Moreover, the trial’s design and outcomes emphasize the evolving understanding of immunotherapy’s role in cancer treatment, she continues. Initially, it was unclear whether checkpoint inhibitors would provide widespread benefits across all patients with metastatic TNBC, Tolaney says. However, the KEYNOTE-355 trial has clarified that the presence of PD-L1 is a crucial biomarker for predicting response to pembrolizumab, guiding more effective and tailored treatment approaches, Tolaney concludes.