Chemotherapy remains effective in ALK-TKI therapy: a retrospective analysis in ALK-positive advanced NSCLC

Abstract

Tyrosine kinase inhibitors (TKIs) are the standard therapy for advanced non-small cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) fusions. However, acquired resistance remains a major challenge, necessitating strategies to prolong therapeutic efficacy. This study retrospectively analyzed 109 patients with ALK fusion-positive NSCLC treated with crizotinib, comparing survival outcomes between those who received chemotherapy as first- or second-line treatment and those who did not. We further evaluate the impact of different sequential treatment strategies involving ALK-TKIs and chemotherapy. Progression‑free survival 1 (PFS 1 ) is defined as the time from first‑line treatment initiation to disease progression on first‑line therapy. Progression‑free survival 2 (PFS 2 ) is defined as the time from first‑line treatment initiation to disease progression on second‑line therapy or death from any cause. Kaplan–Meier analysis and Cox proportional hazards models assess survival probabilities and prognostic factors for overall survival (OS) and PFS 2 . Patients who had received chemotherapy demonstrated significantly longer median PFS 2 compared to those who had not (29.9 vs. 23.4 months, P = 0.039). Likewise, median OS was markedly prolonged in the sequential therapy group (78.7 vs. 43.0 months, P = 0.026). Patients who initially received chemotherapy exhibited a significantly longer median PFS 2 (37.5 vs. 24.7 months, P = 0.045). However, the median OS in the TKI-first sequential group was not reached, and the difference between treatment sequences was not statistically significant. In ALK fusion-positive NSCLC, additional chemotherapy confers a significant survival advantage. However, the difference in survival outcomes between treatment sequences was not statistically significant.