Next-generation Sequencing Unlocks New Options in Refractory Sarcomatoid Mesothelioma: A Case Report

Abstract Sarcomatoid mesothelioma is a rare and aggressive malignancy with limited response to standard therapies. We report the case of a patient with metastatic sarcomatoid mesothelioma harboring KRAS G12C and ERBB2 mutations. After failing chemotherapy and immunotherapy, the patient received sotorasib and later trastuzumab deruxtecan, resulting in mixed but durable responses. This case highlights the value of next-generation sequencing in guiding personalized treatment for rare treatment-refractory malignancies and supports the application of precision oncology even in histologies not traditionally associated with targetable alterations.