1527P Assessing clinical benefit of olaparib maintenance treatment in subgroups of patients with germline BRCA mutation (gBRCAm) and metastatic pancreatic cancer: Phase III POLO trial

The phase III POLO trial showed that in patients with metastatic pancreatic cancer (mPC) and a germline BRCA mutation (gBRCAm) who had not progressed on platinum-based chemotherapy (PBC), progression-free survival (PFS) was significantly longer with maintenance olaparib than with placebo (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.35, 0.82; median 7.4 months vs 3.8 months), with pre-specified subgroup analyses showing consistency (Golan et al. NEJM 2019). Additional pre-specified and post hoc subgroup, sensitivity and multivariate analyses further assessed consistency with primary PFS. Participants had received first-line PBC for ≥ 16 weeks and were randomized 3:2 to maintenance olaparib 300 mg bid or placebo. The primary endpoint was PFS by blinded independent central review. Subgroup analyses assessed treatment effect consistency with the primary endpoint of PFS; multivariate analyses assessed impact of baseline factors; sensitivity analyses assessed evaluation time (scan frequency) and deviation (protocol deviation) biases. All pre-specified and post hoc subgroup analyses showed PFS benefits with olaparib versus placebo were consistent with primary PFS, including for patients stratified by Eastern Cooperative Oncology Group (ECOG) status, dose interruptions, previous primary malignancies, liver metastasis and location (table). Multivariate analyses demonstrated a PFS improvement with olaparib versus placebo when adjusted for baseline factors, while sensitivity analyses showed no indication of bias (table).Table:PFS analysisOlaparib, NPlacebo, NHR95% CIPrimary/pre-specified/full analysis setPrimary92620.530.35, 0.82Post hoc/exploratory subgroupECOG status at baselineNormal65380.610.38, 1.01Restricted25230.460.23, 0.91Dose interruption38100.610.28, 1.53No dose interruption52510.570.35, 0.93Previous primary malignancy29120.610.28, 1.49No previous primary malignancy63500.550.35, 0.87Liver metastasis61480.610.39, 0.97Europe49390.590.35, 1.00MultivariateAdjusted for 13 baseline factors83560.540.36, 0.82SensitivityEvaluation time bias92620.550.36, 0.85Deviation bias71490.470.29, 0.76 Open table in a new tab Maintenance olaparib provided a consistent, significant PFS benefit versus placebo in patients with mPC and a gBRCAm who had not progressed on PBC, irrespective of clinical factors, geographical location or other baseline factors.