Response and acquired resistance to savolitinib in a patient with pulmonary sarcomatoid carcinoma harboring MET exon 14 skipping mutation: a case report

• Main Authors: Han S, Fang J, Lu S, Wang L, Li J, Cheng M, Ren Y, Su W
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-09-01
• Series: OncoTargets and Therapy
• Subjects: Targeted therapy; Tumor response; Acquired resistance; Lung cancer
• Online Access: https://www.dovepress.com/response-and-acquired-resistance-to-savolitinib-in-a-patient-with-pulm-peer-reviewed-article-OTT

Sen Han,1 Jian Fang,1 Shun Lu,2 Linfang Wang,3 Jing Li,3 Min Cheng,3 Yongxin Ren,3 Weiguo Su3 1Department of Thoracic Oncology Ii, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Hutchison MediPharma Limited, Shanghai, People’s Republic of ChinaCorrespondence: Jian FangDepartment of Thoracic Oncology II, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, People’s Republic of ChinaTel [phone]Fax +86 10 8 819 6478Email [e-mail]: 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