Efficacy and safety of adjuvant ensartinib in stage I ALK-positive NSCLC patients: a retrospective, multicenter study

BackgroundThe role of adjuvant Ensartinib in patients with stage I ALK-positive non-small cell lung cancer (NSCLC) who exhibit high-risk pathological features remains unclear. This multicenter retrospective study aimed to evaluate the efficacy and safety of adjuvant Ensartinib in this population.MethodsA total of 393 patients with completely resected stage I ALK-positive NSCLC were enrolled from five centers in China between March 2017 and January 2026. Patients were categorized into the Ensartinib group (n=63) and the observation group (n=330). Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were employed to balance baseline characteristics. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety.ResultsAfter IPTW, baseline characteristics were well balanced between groups. The Ensartinib group exhibited a significantly improved 3-year DFS compared to the observation group (100% vs. 90.2%; P=0.014). This benefit was particularly pronounced in patients with high-risk pathological features (micropapillary or solid subtypes or complex glandular pathological subtypes ≥10%, mucinous adenocarcinoma, or spread through air spaces), where the 3-year DFS was 100% in the Ensartinib group versus 86.5% in the observation group (P=0.016). No significant difference in OS was observed between groups. Adverse events were reported in 87.3% of patients in the Ensartinib group, all of which were grade 1–2, with rash being the most common adverse event (85.7%).ConclusionAdjuvant Ensartinib significantly improves DFS in stage I ALK-positive NSCLC patients exhibiting high-risk pathological features, while demonstrating a favorable safety profile. For patients devoid of high-risk factors, observation remains a reasonable strategy. These findings support individualized adjuvant treatment based on pathological risk stratification.