Sustained Clinical Response to Olaparib in a Patient with Metastatic Pancreatic Cancer and Somatic ATM Mutation R2034Ter: A Case Report.

Abstract

Introduction: Pancreatic cancer remains a lethal disease with limited therapeutic options. Treatment with PARP inhibitors has been successfully described mainly in patients with germline mutation in BRCA1/2. The efficacy of PARP inhibitors in patients with alterations in other genes in the homologous repair pathway is under discussion.

Case presentation: A 77-year-old male patient with metastatic pancreatic ductal adenocarcinoma (PDAC) was initially treated with 5-fluoruracil, oxaliplatin, and irinotecan, followed by 5-floururacil and irinotecan over the course of 1 year, leading to sustained partial remission. Molecular genetic analysis of the tumor revealed an inactivating R2034Ter mutation in the ataxia telangiectasia serine/threonine kinase gene (ATM), being part of a homologous DNA damage repair pathway eventually involving BRCA1 and BRCA2. After discussion in the molecular tumor board, the patient received off-label olaparib maintenance therapy, under which disease was stable over a period of 18 months. After developing one new liver metastasis at 21 months on olaparib, he received conventional therapy with gemcitabine/cisplatin to which he responded.

Conclusion: This is the first case of an R2034Ter ATM mutant PDAC with sustained clinical response under olaparib maintenance therapy reported. In select cases, ATM, a member of the BRCA pathway, might be a druggable target in pancreatic cancer.