KEYLYNK-009: Pembrolizumab plus Olaparib in Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer after Clinical Benefit from First-Line Pembrolizumab plus Chemotherapy.

Pembrolizumab plus olaparib versus pembrolizumab plus chemotherapy was evaluated as postinduction therapy for patients with PD-L1-unselected locally recurrent inoperable/metastatic triple-negative breast cancer (TNBC) who derived clinical benefit from first-line pembrolizumab plus platinum-based chemotherapy induction therapy. In this phase 2 study (NCT04191135), participants with previously untreated locally recurrent inoperable/metastatic TNBC received first-line pembrolizumab 200 mg once every 3 weeks plus platinum-based chemotherapy. Participants with complete/partial response or stable disease (per RECIST v1.1) were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks plus olaparib 300 mg twice a day or pembrolizumab plus chemotherapy. Progression-free survival (PFS) and overall survival (OS) were primary endpoints. Of 460 participants receiving induction treatment, 271 were randomly assigned to postinduction therapy. The median PFS was 5.5 months in the pembrolizumab plus olaparib group versus 5.6 months in the pembrolizumab plus chemotherapy group [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.72-1.33; P = 0.4556]. The median OS was 25.1 versus 23.4 months, respectively (HR, 0.95; 95% CI, 0.64-1.40). In participants with tumor BRCA1/BRCA2 mutations (tBRCAm), HRs for PFS (HR, 0.70; 95% CI, 0.33-1.48) and OS (0.81; 95% CI, 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. Although the primary endpoint was not met, postinduction pembrolizumab plus olaparib therapy resulted in similar PFS and OS compared with pembrolizumab plus chemotherapy in this setting. The positive trend for PFS and OS in participants with tBRCAm suggests a potential nonchemotherapy strategy for maintaining clinical benefit attained with first-line pembrolizumab plus chemotherapy induction treatment. No new safety signals were identified.