Efficacy of alectinib in advanced ALK-positive non-small cell lung cancer: Results from the Russian multicenter KARL-005 study

Abstract

Introduction. Tyrosine kinase inhibitors, specifically alectinib, have significantly improved the prognosis for patients with advanced ALK-positive non-small cell lung cancer (ALK+ aNSCLC). National multicenter real-world data are essential to validate these outcomes within a broader clinical population. Aim. To evaluate the clinical efficacy of first-line alectinib in patients with ALK+ aNSCLC within routine clinical practice in the Russian Federation. Materials and methods. This multicenter retrospective study included patients who initiated first-line alectinib between 2020 and 2022. Primary endpoints included progression-free survival (PFS) and overall survival (OS) in the first-line setting. Secondary objectives assessed the prevalence of comorbidities and alectinib efficacy across clinical subgroups. Results. Data from 153 patients across 12 centers were analyzed. The median age was 56.7 years (range: 25.0–82.9), and 59.5% were female. At baseline, 21% of patients had an ECOG PS ≥ 2, and 20.3% presented with CNS metastases. Alectinib was administered as first-line therapy in 79 patients (51.6%), while 74 patients received it following prior chemotherapy. With a median follow-up of 47.8 months, the median PFS was 53.6 months (95% CI: 37.2 – NR) in the first-line cohort and 55.6 months (95% CI: 31.9 – NR) in the post-chemotherapy cohort. In the first-line group, median OS was not reached (5-year OS: 63.2%). For the post-chemotherapy group, median OS was 66.5 months (95% CI: 48.2 – NR; 5-year OS: 51.2%). Comorbidities were prevalent, notably cardiovascular disease (64.1%) and metabolic disorders (21.6%). Conclusion. Alectinib efficacy in Russian routine practice is comparable to the results of the landmark ALEX trial. The high prevalence of comorbidities highlights the need for a comprehensive, individualized approach to therapy selection in this population.