Efficacy and safety of neoadjuvant targeted therapy in surgically treated patients with ALK-rearranged non-small cell lung cancer.

Background: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have demonstrated substantial efficacy in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but evidence for their use in the neoadjuvant setting remains limited. This study aimed to evaluate and compare the efficacy and safety of neoadjuvant ALK-targeted therapy and chemotherapy-based neoadjuvant treatment in surgically treated patients with ALK-rearranged NSCLC. Methods: We retrospectively analyzed the clinical data of 20 patients with ALK-rearranged NSCLC who received neoadjuvant therapy followed by curative-intent surgery at the Department of Thoracic Surgery, Hunan Cancer Hospital, between October 2018 and April 2025. Patients were retrospectively classified into an ALK-TKI group (n=13) and a chemotherapy-based group (n=7) according to the neoadjuvant regimen received. A comparative analysis assessed radiological response, pathological response, postoperative complications, adverse events, and survival outcomes between the 2 groups after neoadjuvant therapy. Results: The baseline characteristics of the 2 groups were comparable without statistically significant differences. Among the 13 patients in the ALK-TKI group, 9 achieved partial response (PR) and 4 had stable disease (SD), resulting in an objective response rate (ORR) of 69.2%. Among the 7 patients in the chemotherapy-based group, 3 achieved PR and 4 had SD, resulting in an ORR of 42.9% (P=0.35). Six patients (46.2%) in the ALK-TKI group and one patient (14.3%) in the chemotherapy-based group achieved major pathological response (MPR) (P=0.32). Four patients (30.8%) in the ALK-TKI group and one patient (14.3%) in the chemotherapy-based group achieved pathological complete response (pCR) (P=0.61). The proportion of patients with ypN0 disease was significantly higher in the ALK-TKI group than in the chemotherapy-based group (11/13 vs. 3/7, P=0.043), and the extent of pathological nodal downstaging was also greater in the ALK-TKI group (P=0.008). There were no significant differences between the 2 groups in the incidence of adverse events, grade ≥3 adverse events, postoperative complications, surgical approach, operative time, blood loss, thoracic drainage duration, or postoperative hospital stay. Kaplan-Meier analyses showed nonsignificant numerical trends toward improved overall survival and recurrence-free survival in the ALK-TKI group. However, these findings were based on a small number of recurrence and death events and should be interpreted with caution. Conclusions: Neoadjuvant ALK-TKI therapy showed numerically higher radiological and pathological response rates and a significantly higher ypN0 rate and greater pathological nodal downstaging relative to the baseline clinical nodal stage compared with chemotherapy-based neoadjuvant therapy. No statistically significant differences in the observed safety or perioperative outcomes were identified between the groups.