Long-term survival with adaptive dual-targeted therapy in an epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patient with mesenchymal-epithelial transition (MET) amplification guided by minimal residual disease (MRD) assessments: a case report and literature review.

Abstract

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved great success in the treatment of non-small cell lung cancer (NSCLC) with activating EGFR mutations. However, acquired resistance is a major obstacle to long-term disease remission in clinical practice. Mesenchymal-epithelial transition (MET) gene amplification has been identified as a key resistance mechanism to first- and second-generation EGFR-TKIs.

Case description: We report the case of a 65-year-old female patient with advanced lung adenocarcinoma (LUAD) who developed bone and adrenal gland metastases following treatment with gefitinib. Next-generation sequencing (NGS) of a biopsy specimen revealed the co-occurrence of MET amplification and EGFR exon 19 deletion mutation. The combined treatment of savolitinib and gefitinib effectively controlled the disease, resulting in a favorable long-term clinical outcome. With continued follow-up through April 2025, the patient has maintained progression-free survival (PFS) over 8 years. However, monitoring revealed the patient had grade 4 peripheral edema, and negative circulating tumor DNA (ctDNA), which necessitated a savolitinib dose reduction. Subsequent minimal residual disease (MRD) assessments and radiological scans revealed a remarkable therapeutic response with sustained efficacy.

Conclusions: We report the first case of a LUAD patient with MET amplification and EGFR exon 19 deletion mutation who achieved a durable response with targeted therapy. ctDNA monitoring enabled precise dose modulation that balanced therapeutic efficacy with toxicity management. This case establishes a paradigm for chronic cancer management, demonstrating that integrating molecular diagnostics with dynamic treatment optimization can effectively convert aggressive malignancies into manageable chronic conditions while preserving the quality of life of patients.