Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and poorly differentiated type of non-small cell lung cancer (NSCLC) with specific characteristics, which usually presents a challenge in clinical practice. Mesenchymal–epithelial transition (MET ) gene has been identified as a promising target for treatments in the past few years. Here, we report a case of a patient with PSC harboring MET  exon 14 mutation, who responded to a novel MET inhibitor – savolitinib.
Case presentation: A 75-year-old male patient with symptoms of cough, dyspnea and intermittent chest pain was diagnosed with sarcomatoid carcinoma. The tumor involved the right lung, the right hilum and multiple lesions in the right pleura, indicating a clinical disease stage IV. Next-generation sequencing of lung biopsy specimen indicated a MET  exon 14 skipping mutation (NM_000245:c.3028+3A>G), with a variant allele frequency of 73.9%. The patient achieved a rapid and durable partial response with the initiation of savolitinib administration (600 mg, orally, once daily). The progression-free survival in this patient was 36 weeks. There were no ≥grade 3 adverse events reported and there was no dose reduction during treatment. Following savolitinib treatment, the allele frequency of MET  exon 14 mutation in plasma circulating tumor DNA decreased with the reduction in tumor size. At the time of disease progression, fibroblast growth factor receptor 1 (FGFR1 ), EGFR  and KRAS  gene amplification were newly identified in tumor biopsy sample.
Conclusion: This patient with PSC harboring MET  exon 14 skipping mutation achieved significant clinical benefit with savolitinib treatment. Emergence of FGFR1 , EGFR  and KRAS  gene amplification at the time of disease progression was likely responsible for the resistance to savolitinib in this case.
Keywords: targeted therapy, tumor response, acquired resistance, lung cancer