Pembrolizumab and olaparib in homologous-recombination-deficient metastatic pancreatic cancer: the phase 2 POLAR trial - PubMed
5 hours ago
- #immunotherapy
- #pancreatic cancer
- #PARP inhibitor
- The phase 2 POLAR trial evaluated pembrolizumab plus olaparib as maintenance therapy in metastatic pancreatic cancer (PC) with homologous recombination deficiency (HRD).
- Participants were stratified into three cohorts: cohort A (BRCA1/BRCA2 or PALB2-mutated HRD), cohort B (non-core HRD), and cohort C (HRD-wild type, platinum-sensitive).
- Cohort A did not meet the primary endpoints of ≥43% objective response rate (ORR) and ≥77% 6-month progression-free survival (PFS) rate (ORR: 35%, 6-month PFS: 64%).
- Median PFS and overall survival (OS) for cohort A were 8.3 months and 28 months, respectively, with 2-year and 3-year OS rates of 56% and 44%.
- Cohorts B and C showed lower efficacy (ORR: 8% and 14%; median PFS: 4.8 and 3.3 months; median OS: 18 and 10 months).
- Translational analyses linked circulating tumor DNA response, tumor-infiltrating lymphocytes, and frameshift indel neoantigens to durable clinical benefit.
- The study suggests a subset of HRD PC may benefit from PARP-ICB maintenance, supporting biomarker-guided immunotherapy strategies.