Long-term outcomes and clinical features of stage III non-small-cell lung cancer harboring ALK rearrangements: a multicenter retrospective study of 176 patients

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Stage III non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase ( ALK ) gene rearrangements requires multimodal therapy. The ALINA trial demonstrated the efficacy of adjuvant ALK tyrosine kinase inhibitors ( ALK TKIs) in early-stage ALK -positive NSCLC but provided limited long-term data for stage III patients. Real-world evidence is needed to validate and expand these findings. This multicenter, real-world cohort study analyzed treatment patterns and clinical outcomes in 176 patients with stage III ALK -positive NSCLC. The prognosis of different EML4-ALK variants was evaluated. Inverse probability treatment weighting (IPTW) and sensitivity analyses were performed to adjust for the confounding factors. At a median follow-up of 48.9 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 71.9 % and 14.8 %, respectively, with a median PFS of 19.5 months. Among all 176 patients, 144 (81.8 %) received definitive local therapy, including 132 who underwent surgery and 12 who received definitive chemoradiotherapy (CRT); the remaining 32 patients (18.2 %) received systemic therapy alone. The most common EML4 - ALK variants were v1 (25.3 % of patients, n = 23) and v3 (38.5 % of patients, n = 35). EML4-ALK v1 variants was associated with significantly better OS compared to other variants ( P < 0.05). A total of 126 (71.6 %) patients relapsed, and 97 (55.1 %) had distant metastasis. Local treatment (HR = 0.33, 95 % CI: 0.15–0.73; P = 0.007) and targeted therapy (HR = 0.34, 95 % CI: 0.17–0.69; P = 0.003) were significant independent prognostic factors for better OS. Patients receiving local therapy and adjuvant ALK TKIs achieved 100 % 5-year OS without progression. The sensitivity analysis yielded similar findings. This study provided long-term follow-up data that validated the findings of the ALINA trial. Stage III ALK -positive NSCLC is prone to relapse but local therapy combined with adjuvant ALK TKIs offers a promising strategy. Patients with EML4-ALK v1 mutations may show improved outcomes.