Pembrolizumab plus Chemotherapy Improves Survival in Triple-Negative Breast Cancer

Pembrolizumab, an immune checkpoint inhibitor widely used in many malignancies, was recently shown to benefit select patients with metastatic breast cancer. Researchers now report final results of the industry-sponsored phase 3 KEYNOTE-355 trial, which compared pembrolizumab plus chemotherapy in patients with metastatic, program death ligand 1 (PD-L1)–positive, triple-negative breast cancer (TNBC).

A total of 847 previously untreated patients with metastatic TNBC were randomly assigned (2:1) to pembrolizumab (200 mg every 3 weeks) plus chemotherapy or placebo plus chemotherapy. Chemotherapy options included nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin. PD-L1 status was assessed using the combined positive score (CPS) determined by dividing the number of PD-L1– staining cells (tumor cells, lymphocytes, and macrophages) by the total number of viable tumor cells multiplied by 100; a score of ≥10 was considered positive.

Median follow-up was 44.1 months. Among patients with CPS ≥10, median progression-free survival (PFS) was significantly higher in the pembrolizumab arm compared with the placebo arm (9.7 vs. 5.6 months) as was median overall survival (OS; 23.0 vs. 16.1 months). Among patients with CPS >1, median OS did not differ between the two treatment groups, but PFS showed a modest 2-month improvement in the pembrolizumab arm (7.6 vs. 5.6 months).

Overall adverse event rates were similar between the treatment arms, however immune-mediated adverse events occurred in 26.5% of pembrolizumab recipients versus 6.4% of placebo recipients, the most common being hypo- or hyperthyroidism. No immune toxicity-related deaths occurred.