An evaluation of olaparib for the treatment of pancreatic cancer

Abstract

Introduction: Advanced pancreatic cancer remains a lethal, incurable malignancy. Chemotherapy is the mainstay of systemic therapy consideration in metastatic pancreas cancer. Homologous recombinant DNA repair mutations are reported in about 7% of pancreas cancer cases and have rapidly emerged as actionable mutations.

Areas covered: A review was conducted of publications of PARP inhibitors in pancreatic malignancies with a focus on clinical trials with olaparib. This included a review of the phase II and phase III clinical trials of olaparib in pancreatic cancer.

Expert opinion: Olaparib was compared to placebo in a randomized double blind trial in cases with advanced pancreatic cancer and germline BRCA1/2 mutations, with a clinical response or stable disease after at least 16 weeks of platinum based chemotherapy. Olaparib significantly improved progression free survival, [HR = -.53, p = 0.0035] but did not improve overall survival. No differences in quality of life were noted between the two arms. Adverse events from olaparib were noted in 40% of treated patients. Objective response rate was 20% in olaparib arm and 10% in placebo treated arm. A careful consideration of the risks and benefits of this personalized therapy is advisable, prior to clinical application in germline BRCA1/2 mutated advanced pancreatic cancer.

Keywords: BRCA1/2; PARP; homologous repair; pancreas cancer.