Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer

Although systemic therapy for metastatic pancreatic cancer has improved, overall survival (OS) is still less than 1 year, and no targeted or immunotherapy agents have been approved to treat this disease. Investigators now report results of the industry-sponsored, international, double-blind, randomized, controlled, phase III POLO trial evaluating the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib in patients with a BRCA germline mutation and metastatic pancreatic cancer.

Patients had to demonstrate stable disease or response to platinum-based chemotherapy for at least 4 months. Of 3315 patients screened for BRCA mutation, 247 patients tested positive. Of these, 154 (4.6% of the total; median age, 57 years) met eligibility criteria and were assigned 3:2 to receive maintenance olaparib or placebo. Nearly three quarters had BRCA2 mutation, and about a quarter had BRCA1 mutation. More than 80% of patients had received prior FOLFIRINOX (median duration, approximately 5 months); half had prior response to chemotherapy, and half had stable disease.

Progression-free survival (PFS; the primary endpoint) was prolonged with olaparib versus placebo (7.4 vs. 3.8 months; hazard ratio, 0.53; P=0.004); however, OS was similar (18.1 and 18.9 months, respectively), and only 14.5% of placebo recipients crossed over to a PARP inhibitor after disease progression. Responses to olaparib and placebo were seen in 23% and 12%, respectively, with a higher duration of response to olaparib (24.9 vs. 3.7 months). Quality of life was similar with olaparib or placebo, and no new safety signals were observed.