Neoadjuvant ALK tyrosine kinase inhibitor in patients with resectable locally advanced non-small cell lung cancer harboring ALK rearrangement.

Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have demonstrated superior efficacy compared with chemotherapy in ALK-positive non-small cell lung cancer (NSCLC) in both first-line and adjuvant settings; however, evidence supporting their use as neoadjuvant therapy in locally advanced disease remains limited. This retrospective study analyzed the clinicodemographic characteristics, treatment details, and toxicities of patients with locally advanced ALK-positive NSCLC who received neoadjuvant ALK-TKI monotherapy. The objective response rate (ORR), radical resection (R0) rate, and pathological response were evaluated, along with disease-free survival (DFS), overall survival, and the optimal duration of neoadjuvant treatment. A total of 25 patients were included, with a median age of 49 years; 48.0% were female, 68.0% were never-smokers, and 84.0% harbored EML4-ALK rearrangements. The median duration of neoadjuvant therapy was 5 months. The most common treatment-related adverse events were edema, nausea, and constipation, and grade 3 events occurred in 24% of patients. The ORR reached 92.0%, including 22 partial responses and 1 complete response (CR), and all patients underwent R0 resection. Pathological evaluation showed that 32.0% achieved a pathological CR and 36.0% achieved a major pathological response. The optimal neoadjuvant treatment duration was preliminarily defined as 4-6 months, based on a locally estimated scatterplot smoothing (LOESS) analysis of both pathological response and toxicity profiles. With postoperative follow-up ranging from 11 to 57 months, the 3-year DFS rate was 76.2%, and only one patient died due to intracranial hemorrhage secondary to brain metastasis. Overall, neoadjuvant ALK-TKI monotherapy showed promising efficacy and a manageable safety profile in locally advanced ALK-positive NSCLC, providing preliminary support for its further investigation in prospective trials.