Real-world use of PARP inhibitors in BRCA1/2-mutated pancreatic cancer: A retrospective analysis.

Abstract

599 Background: BRCA1 or BRCA2 mutations can be found in approximately 6 to 8 percent of patients patients with metastatic pancreatic adenocarcinoma (mPaC). Olaparib is the only PARP inhibitor (PARPi) approved in the EU and the US as maintenance treatment for biomarker-selected patients with mPaC in the 1st line platinum-sensitive setting. However, treatment sequencing can be heterogeneous, and there is a lack of real-world data on patterns of PARPi use in relation to platinum use in BRCA1/2-mutated mPaC. Methods: Longitudinal records collected between 1/2012-12/2020 were analyzed for a cohort of 55 mPaC patients with BRCA1 or BRCA2 mutations identified by commercial NGS testing who enrolled in Perthera’s US real-world observational registry study. Treatment patterns including PARPi utilization and platinum-sensitivity (16 weeks without progression at any point within known history) were abstracted via physician notes across all lines of therapy. Results: PARPi use was documented in 60% (N=33) of 55 patients with BRCA1/2-mutated mPaC in any treatment setting. Within this cohort, 21 patients received a single agent PARPi outside of clinical trials. Among these patients, only 38% (8 of 21) transitioned to a PARPi in a platinum-sensitive context, and only 14% (3 of 21) of these transitions occurred before 2nd line. Notably, 6 patients received a PARPi in the platinum-resistant setting. Within the broader cohort, platinum-sensitive criteria was fully met for 73% (40 of 55); however, only 49% (27 of 55) reached this milestone of platinum-sensitivity prior to initiating a 2nd line therapy. Conclusions: The majority of these BRCA1/2-mutated patients received a PARPi-based therapy in a variety of contexts with respect to line of therapy and prior platinum history. These findings highlight the value of upfront genetic and molecular testing and the need for further exploration to identify factors associated with treatment response as well as optimized treatment sequencing.