Presence of MET exon 14 skipping and fusion as mechanism of osimertinb resistance in a lung adenocarcinoma with an EGFR exon 19 deletion that responds to combination of capmatinib and osimertinb: A case report

Heliyon. 2023 Nov 18;9(11):e22515. doi: 10.1016/j.heliyon.2023.e22515. eCollection 2023 Nov.

Abstract

Lung cancer stands as a leading cause of mortality in China, with EGFR mutations frequently identified as pivotal driver genes. Osimertinib, a tyrosine kinase inhibitor targeting EGFR mutations, is typically employed as a first-line treatment for EGFR-sensitive mutations; nevertheless, resistance can emerge. In this case report, we present the case of a 53-year-old non-smoking male diagnosed with stage IV lung adenocarcinoma bearing an EGFR exon 19 deletion. This patient eventually developed resistance to both Erlotinib and Osimertinib after 28 months of treatment. Subsequent genetic testing uncovered the emergence of new MET exon 14 skipping and MET fusion, coexisting with the initial EGFR exon 19 deletion. In light of this complex molecular profile, the patient was administered a combination therapy consisting of Osimertinib and Capmatinib. This novel approach yielded a partial response, and notably, the patient experienced a progression-free survival exceeding 7 months. Vigilant monitoring of the patient's progress revealed the disappearance of the MET exon 14 skipping and a notable improvement in the patient's symptoms. This case report underscores the potential efficacy of Osimertinib and Capmatinib combination therapy as a viable treatment strategy for patients harboring EGFR-mutated lung cancer who develop resistance to first-line EGFR inhibitors due to MET activation.

Keywords: Capmatinib; EGFR; MET exon 14 skipping; MET fusion; NSCLC; Osimertinib; Resistance mechanism.

Publication types

  • Case Reports