Sustained clinical response to Olaparib in a patient with metastatic pancreatic cancer and somatic ATM-Mutation R2034Ter: a case report.

Abstract

Background Pancreatic cancer remains a lethal disease with limited therapeutic options. The field of targeted therapies is still growing. Treatment with PARP inhibitors has been successfully described mainly in patients with germline mutation in 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 one 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 (MTB), the patient was started on off-label Olaparib maintenance therapy, under which he has shown stable disease over a period of eighteen 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 a 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.