Multinational phase 2 study of pembrolizumab-olaparib for advanced TNBC after clinical benefit from first-line pembrolizumab-chemotherapy

The multinational phase 2 KEYLYNK-009 trial evaluated pembrolizumab plus olaparib versus pembrolizumab plus chemotherapy as postinduction therapy for patients with PD-L1-unselected locally recurrent inoperable of metastatic triple-negative breast cancer (TNBC) who derived clinical benefit from first-line pembrolizumab plus platinum-based chemotherapy induction. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Of 460 participants receiving induction treatment, 271 were randomly assigned to postinduction therapy. The median PFS was 5.5 months with pembrolizumab-olaparib versus 5.6 months with pembrolizumab-chemotherapy (HR 0.98; 95% CI 0.72-1.33) and the median OS was 25.1 months versus 23.4 months, respectively (0.95; 0.74-1.40); in participants with BRCA1/2 mutations, HRs for PFS (0.70; 0.33-1.48) and OS (0.81; 0.28-2.37) favored pembrolizumab plus olaparib. Treatment-related adverse events occurred in 84.4% and 96.2% of participants receiving pembrolizumab plus olaparib and pembrolizumab plus chemotherapy, respectively. The authors conclude that the primary endpoint was not met, but that postinduction pembrolizumab plus olaparib resulted in similar PFS and OS compared with pembrolizumab plus chemotherapy. The positive trend for PFS and OS in participants with BRCA1/2 mutations suggests a potential nonchemotherapy strategy for maintaining clinical benefit attained with pembrolizumab plus chemotherapy induction treatment.