Analysis of Clinical Features and Treatment Strategies in Advanced Lung Adenocarcinoma Patients With Acquired ALK Fusion After Resistance of EGFR-TKIs

Abstract

Background The mechanism of secondary drug resistance in advanced Non Small Cell Lung Cancer(NSCLC) patients with Epidermal Growth Factor Receptor (EGFR) gene sensitive mutation after EGFR-Tyrosine Kinase Inhibitors (TKIs) is complex. Acquired Anaplastic Lymphoma Kinase (ALK) fusion mutation is a rare type, and there are few reports on the clinical characteristics and treatment options for this group of patients. Methods Cases of 820 locally advanced or metastatic EGFR-sensitive mutations NSCLC patients whose gene status were detected by Next Generation Sequencing(NGS)after EGFR-TKIs resistance were retrospectively collected. Acquired ALK fusion gene mutation occurred in 4 of them. The clinical information, pathological types, gene mutation status, treatment plans, efficacies and prognoses of these 4 cases were analyzed. Results All 4 patients had lung adenocarcinoma. Three had EML4-ALK fusion and 1 had STRN-ALK fusion. EGFR gene mutation was detected negative in 2 cases after drug resistance, and the abundance of EGFR gene mutation decreased in 2 cases. The Progression Free Survival (PFS) of EGFR-TKIs ranged from 6 to 21 months, and after acquired ALK mutation objective response was all achieved using ALK-TKIs alone or the combination of ALK-TKIs and EGFR-TKIs, with PFS all exceeding 6 months. One patient developed small cell lung cancer transformation after ALK-TKIs resistance. Conclusion Acquired ALK fusion as a resistant mechanism of EGFR-TKIs is present and rare. EGFR is undetectable or abundance decreased when ALK fusion emerges. ALK-TKIs alone and ALK-TKIs combined with EGFR-TKIs are alternative treatment choices.