Summary
The POLO trial demonstrated that maintenance olaparib significantly improves progression-free survival compared with placebo in patients with germline BRCA-mutated metastatic pancreatic cancer who have not progressed after first-line platinum-based chemotherapy [2]. However, an interim analysis of overall survival showed no statistically significant difference between the two groups [2].
Evidence
**Trial Design**: The POLO trial was a randomized, double-blind, placebo-controlled, phase 3 study conducted in patients with metastatic pancreatic cancer and a germline BRCA1 or BRCA2 mutation whose disease had not progressed during first-line platinum-based chemotherapy [2].
**Population**: Of 3315 screened patients, 154 were randomized (92 to olaparib, 62 to placebo) [2].
**Intervention**: Maintenance olaparib (300 mg twice daily) versus placebo [2].
**Endpoints and Results**: The primary endpoint was progression-free survival (PFS), assessed by blinded independent central review. Median PFS was significantly longer with olaparib than with placebo (7.4 months vs. 3.8 months; hazard ratio for disease progression or death, 0.53; 95% CI, 0.35 to 0.82; P = 0.004) [2]. An interim analysis of overall survival (at 46% data maturity) showed no significant difference (median 18.9 months vs. 18.1 months; hazard ratio for death, 0.91; 95% CI, 0.56 to 1.46; P = 0.68) [2].
**Safety**: Grade 3 or higher adverse events occurred in 40% of the olaparib group versus 23% of the placebo group; 5% and 2% discontinued due to adverse events, respectively [2].
Caveats
The overall survival benefit was not demonstrated in this interim analysis, which may be limited by low data maturity (46%) and a small sample size (n=154) [2]. The evidence is restricted to patients with germline BRCA mutations who have achieved disease control on prior platinum-based chemotherapy; it does not apply to the broader metastatic pancreatic cancer population or other genetic subgroups [2].