Abstract
BACKGROUND: Clinical trials have demonstrated the efficacy of both alectinib and crizotinib in anaplastic lymphoma kinase (ALK) fusion (ALK-positive) non-small cell lung cancer (NSCLC). However, a critical question persists regarding their real-world comparative effectiveness in Chinese patients, especially in light of divergent overall survival (OS) results from Western and Asian trials. To address this uncertainty, this real-world study aimed to directly compare the efficacy of alectinib and crizotinib as first-line therapies in a Chinese clinical setting. METHODS: Patients diagnosed with ALK-positive NSCLC from two centers in China were included in the study. Progression-free survival (PFS) was the primary endpoint, while OS, the disease control rate, the objective response rate, and safety were the secondary endpoints. Second-line therapy and prognostic factors were also investigated. RESULTS: In total, 261 treatment-naïve patients were evaluated, of whom, 128 received crizotinib, and 133 received alectinib. Compared with crizotinib, alectinib demonstrated significant superiority in terms of PFS [45.5 vs. 16.6 months, hazard ratio (HR) =0.36, P<0.001]. However, the PFS of the patients who received first-line alectinib therapy was comparable to that of the patients who received both first-line crizotinib therapy and second-line therapy (45.5 vs. 43.9 months, P=0.32). Similarly, the OS was comparable between the alectinib and crizotinib treatment groups (alectinib vs. crizotinib, not reached vs. 71.2 months, P=0.23). The alectinib treatment group also had a lower incidence of adverse events (AEs) than the crizotinib treatment group (34.6% vs. 50.0%, P=0.01). The occurrence rates of grade 3 or higher AEs were comparable between the two groups (alectinib vs. crizotinib, 4.5% vs. 5.5%). Further, receiving crizotinib instead of alectinib as the first-line therapy and the presence of bone and adrenal metastases at the baseline were independent risk factors for PFS. While the presence of bone, liver, and adrenal metastasis were independent risk factors for OS. CONCLUSIONS: Alectinib is recommended over crizotinib in the treatment of patients with ALK-positive NSCLC.