Sustained Response to Olaparib in a Patient with BRCA2-Mutated Diffuse Pleural Mesothelioma: A Case Report

Abstract Diffuse pleural mesothelioma (DPM) is a rare and aggressive malignancy most often associated with asbestos exposure. Despite multimodal therapy, prognosis remains poor and treatment options in older patients with multiple co-morbidities are limited. Recent advances in tumor genomic profiling have identified several mutations in DPM, although none are currently associated with therapeutic implications. We report the case of an 87-year-old woman with a history of occupational asbestos exposure who was diagnosed with epithelioid diffuse pleural mesothelioma. Next-generation sequencing (NGS) of tumor tissue identified a pathogenic BRCA2 mutation, with subsequent germline testing confirming the same variant as a pathogenic germline BRCA2 mutation. Given her age and comorbidities, Olaparib was initiated as a targeted therapy after poor tolerance to one cycle of platinum and Pemetrexed. The treatment with Olaparib was well tolerated and resulted in both symptomatic and radiological improvement. This case highlights the potential clinical benefit of poly(ADP-ribose) polymerase (PARP) inhibition in selected patients with mesothelioma, particularly those harboring DNA repair defects or those unable to tolerate conventional therapy. Broader incorporation of genomic profiling into routine evaluation of mesothelioma may help identify rare but clinically meaningful biomarkers that can guide individualized treatment strategies.