MET amplification in diffuse pleural mesothelioma and response to savolitinib: a case report

Pleural mesothelioma (PM) is a rare malignancy globally, most frequently associated with alterations in tumor suppressor genes such as NF2, BAP1 and CDKN2A. In contrast, mutations or amplifications of the MET gene are seldomly reported in PM.

Here, we report the case of a 60-year-old East Asian male without asbestos exposure, never-smoker, diagnosed with advanced PM. The disease proved refractory to multiple lines of therapy, including platinum-based chemotherapy, immunotherapy, intrathoracic instillation and a subsequent individualized regimen comprising intraperitoneal cisplatin plus sintilimab for local disease control and potential immunomodulation synergized with oral anlotinib. Following disease progression accompanied by rapidly accumulating seroperitoneum and pelvic effusion, next-generation sequencing (NGS) of ascitic fluid revealed MET gene amplification, and the subsequent switch to savolitinib controlled the malignant ascites. Unfortunately, the patient died of sudden cardiac and respiratory arrest in December 2023.

This case underscores the critical importance of comprehensive genetic testing in guiding the treatment of advanced PM, particularly after the failure of standard therapies. It illustrates that rare but actionable genomic alterations, such as MET amplification, can be identified through liquid or tissue biopsy and can inform successful targeted treatment strategies, even in a tumor type where such alterations are uncommon. Histological classification combined with molecular profiling remains pivotal for personalized oncology.