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Войти в исследования Oncology research and treatment · 2025
Sustained Clinical Response to Olaparib in a Patient with Metastatic Pancreatic Cancer and Somatic ATM Mutation R2034Ter: A Case Report.
Клинический случайСтатьяНазвание и аннотация: Перевод в очереди
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Vornhülz Marlies, Angelberger Marianne, Sirtl Simon, Philipp Alexander B, Rössler Daniel, Ondrejkova Katarina, Markwardt Daniel, Heinrich Kathrin, Westphalen Christoph Benedikt, Heinemann Volker, Jung Andreas, Rogowski Paul, Niyazi Maximilian, Kleger Alexander, Mayerle Julia, Beyer Georg, Beyer Georg
Аннотация
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.
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.