Background
Patients with homologous-recombination-deficient (HRD) pancreatic cancer respond to platinum chemotherapy and PARP inhibition, but durable benefit is limited. POLAR asked whether adding immune checkpoint blockade to PARP inhibition could deepen and extend that benefit as a chemotherapy-free maintenance strategy.
Design
POLAR is an investigator-initiated phase 2 trial evaluating maintenance pembrolizumab + olaparib in biomarker-stratified metastatic pancreatic cancer. Cohort A enrolled patients with BRCA1/2 or PALB2 alterations.
Results
In cohort A (n=33): median PFS 8.3 months, median OS 28 months, and a 3-year OS rate of 44%.
ctDNA response and enrichment of frameshift indel neoantigens were associated with durable clinical benefit, linking the genomic and immune landscape to outcomes.