Efficacy of olaparib maintenance therapy in <i>BRCA1</i> germline mutations in familial pancreatic cancer patient

Abstract

Pancreatic cancer (PaCa) is one of the most aggressive and unfavourable current oncological diseases. The vast majority of patients have unresectable or metastatic disease at diagnosis. Despite considerable achievements in the drug therapy of most malignant tumours, the immediate and long-term results of the treatment of PaCa still remain extremely unsatisfactory, as overall survival at 5 years does not exceed 10%. The high molecular genetic heterogeneity, which is characteristic of pancreatic adenocarcinomas, the low frequency of driver changes, the diagnostic difficulties, and the rapid progressive deterioration of the general health condition of most patients are just a few of the reasons for the lack of highly specific treatment. Understanding that about 10–15% of pancreatic tumours are a manifestation of genetically determined syndromes has changed the pharmaceutical treatment options for this cohort of patients. BRCA1/2 mutation carrier status is one of these reasons, while the relative risk of PaCa is 2.36 in BRCA1 mutation and 3.34 in BRCA2, respectively. The PARP inhibitor therapy experience and proven efficacy allowed to successfully use this group of drugs in the treatment of BRCA-mutated ovarian and breast cancers. The double-blind, placebo-controlled phase III POLO trial showed the benefit of olaparib as maintenance therapy in BRCA-mutated PaCa. This article presents a clinical case report of the use of olaparib in a patient with familial BRCA1-mutated metastatic PaCa.