Patients with pancreatic cancer (PC) harboring DNA damage repair genes (DDRg) alterations, particularly BRCA1/2, may benefit from olaparib. Although the phase III POLO trial demonstrated improved progression-free survival (PFS) with olaparib as maintenance therapy in germline BRCA-mutated metastatic PC, real-world data, especially in patients with non-BRCA DDR alterations, remain limited. The objective of this study is to evaluate the real-world effectiveness and safety of olaparib in PC patients harboring DDRg alterations. A multicenter, retrospective observational study was conducted across eight Spanish hospitals. Adult patients with PC and DDRg alterations who initiated olaparib between December 2018 and October 2022 were included. Data were extracted from electronic medical records. PFS and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A total of 24 patients were included, most commonly harboring gBRCA2 (58.3%), sBRCA2 (16.7%) or ATM (16.7%) alterations. Among patients receiving olaparib as maintenance therapy (87.5%), the objective response rate (ORR) was 33.3%, the median PFS was 10.4 months (95% CI, 1.7-19.1) and the median OS was 32.9 months (95% CI, 20.1-45.6). At data cutoff, the OS rate >20 months was 71.4% and >30 months was 42.9%. Grade ≥3 AEs occurred in 16.7% of patients. This multicenter real-world study olaparib showed clinical activity and acceptable safety profile in PC patients harboring DDRg mutations, including those beyond BRCA. Further studies are needed to validate these findings and to better identify patients who may benefit from olaparib, particularly those with non-BRCA mutations.
García-Díaz et al. (Mon,) studied this question.