A lung adenocarcinoma patient with co-mutations of MET and EGFR exon20 insertion responded to crizotinib

Abstract

Abstract Background Targeted therapy has revolutionized the treatment of patients with malignancies harboring mutations in driver genes and has brought a favorable survival benefit to the population with actionable oncogenic mutations. In recent years, the MET exon14 skipping mutation has been recognized as a potentially promising therapeutic target in non-small cell lung cancer (NSCLC). These changes are mutually exclusive with molecular drivers such as EGFR, KRAS, HER-2, BRAF, ALK and ROS1. The prevalence rate of coexisting MET exon 14 mutations and EGFR sensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2% (3/1590). However, the coexistence of MET exon 14 mutations with EGFR exon 20 insertion mutations has never been reported and the management of this subtype is not identified. Case presentation A 69-year-old male with a right lung adenocarcinoma (T4N2M0, IIIB) was confirmed to be positive for MET exon 14 skipping (c.3028_3028+1delGGinsTT, 44.4%), MET amplification (copy number 4.4), and EGFR exon 20 insertion (p. N771_H773dup, 22.1%) mutations. After the progression of one cycle of chemotherapy (Pemetrexed 0.8 g d1), the patient was subsequently accepted treatment with Crizotinib (250 mg twice a day) and achieved an important clinical remission for six months until the development of brain metastases. Then, he was submitted to a cycle of anti-programmed cell death-1 (PD-1) therapy after failure of Crizotinib and eventually acquired resistance despite of the high expression of programmed death ligand-1 (PD-L1) and tumor mutational burden (TMB) status. Conclusion This case report provides treatment strategies for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-untreated lung adenocarcinoma patients simultaneously carrying MET alterations and EGFR exon 20 insertion mutations. In addition, the signatures of PD-L1 or TMB expression were not the candidate for predicting the efficacy of immunotherapy in this context.

Keywords

• NCSLC
• MET mutation
• EGFR mutation
• Double mutation
• Crizotinib