Durable clinical benefit from PARP inhibition in a platinum-sensitive, BRCA2-mutated pancreatic cancer patient after earlier progression on placebo treatment on the POLO trial: a case report

Abstract

Metastatic pancreatic adenocarcinoma is a deadly malignancy with limited treatment options. Based on the results of the phase 3 POLO trial, the PARP inhibitor olaparib was approved by the Food and Drug Administration as a maintenance therapy in germline BRCA1- and BRCA2-mutated metastatic pancreatic cancer patients whose cancers had not progressed on first-line platinum-based chemotherapy. While this approval was a step forward, there have been criticisms of the POLO study leaving doubts in the field about the effectiveness of PARP inhibition in pancreatic cancer. Here, we describe a patient with a germline BRCA2-mutated, metastatic pancreatic cancer who was randomized to the placebo-arm of the POLO trial. After progressing on the placebo-arm of the POLO study, her cancer again responded to platinum-based chemotherapy and has since been successfully treated for 4 years with off-protocol maintenance olaparib. The presence of placebo treatment in this case serves as an internal control demonstrating the efficacy of PARP inhibition in this patient. This case highlights the potential of PARP inhibitor maintenance therapy in appropriately selected metastatic pancreatic cancer patients.

Keywords: DNA repair; PARP inhibitor; Pancreatic cancer; case report; targeted therapy.