Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review

In non-small cell lung cancer, the two main genetic alterations are epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. The presence of both mutations in a single patient or genetic mutation discrepancies between primary tumors and metastases is uncommon. Therefore, at present, there are no guidelines on the optimal approach and treatment for this group of patients. This report presents the case of a 58-year-old woman with EGFR-mutated regional lung cancer who underwent surgery followed by adjuvant chemotherapy. Upon disease recurrence, the response to EGFR-tyrosine kinase inhibitor therapy was poor. Further analysis of metastatic pleural fluid revealed an ALK mutation. The patient was then treated with anti-ALK therapy, resulting in long-term disease stability. In conclusion, the coexistence of EGFR and ALK mutations in lung cancer is rare, likely due to tumor heterogeneity and prior treatments. Resistance to targeted therapies can develop through new molecular alterations during disease progression. Re-biopsies at progression are crucial for detecting these changes and optimizing treatment based on the updated molecular profile.