Introduction: Tumor control and survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) has improved with more effective polychemotherapies. The identification of novel therapeutic targets is strongly needed in order to propose maintenance therapies that improve quality of life while maintaining tumor control.
Areas covered: PDAC with mutations in homologous recombination repair genes such as BRCA are particularly sensitive to platinum agents. Recently, the potential role of poly(ADP-ribose) polymerase (PARP) inhibitors was suggested. The POLO study has shown that olaparib was efficient and well-tolerated as maintenance therapy in patients with germline BRCA1/2 mutation and a metastatic PDAC controlled after a platinum-based induction chemotherapy.
Expert opinion: The demonstration of olaparib efficacy in patients with metastatic PDAC and BRCA germline mutation has paved the way for maintenance with a targeted therapy. Further studies are needed to assess; the potential role for PARPI in earlier forms of PDAC, those with somatic or more rare BRACness signatures, to overcome primary or secondary resistances to PARPi, and to combine them with other antitumoral agents.
Keywords: BRCA gene; Cancer; PARP; olaparib; pancreas; parp inhibitor.