Exploration of the favorable duration for neoadjuvant targeted therapy in mutant non-small cell lung cancer

Neoadjuvant-targeted treatment (NTT) has advanced significantly in patients with mutant non-small cell lung cancer (NSCLC) undergoing surgery; however, its favourable duration remains unclear. This real-world study explored the association between NTT duration and therapeutic outcomes. This study retrospectively enrolled multicentre patients with mutant NSCLC who received ≥ 2 NTT cycles followed by complete surgical resection. Correlations among treatment duration, therapeutic responses, and safety were analysed using major pathological response (MPR) as the primary endpoint. Univariate and multivariate logistic regression analyses identified the independent predictors of MPR. Among the 54 patients ultimately included, the objective response rate (ORR) and MPR rate in the overall cohort were 48.1% and 35.2%, respectively. With a median follow-up of 31 months, 12 (22.2%) patients experienced recurrence, and 6 (11.1%) died. Patients who achieved MPR showed longer relapse-free survival (RFS) ( p = 0.023) and overall survival (OS) ( p = 0.048); however, these exploratory findings require validation with a longer follow-up. Notably, patients with 4-cycle treatment demonstrated the highest proportion of MPR cases (73.7%, 14/19 of all patients with MPR). MPR rates differed across the treatment cycle groups, with similar patterns observed in the analyses stratified by disease stage. Multivariate analysis showed that receiving ≥ 4 cycles of NTT remained associated with MPR after adjustment for measured clinicopathological variables [odds ratio (OR) = 8.657, 95% confidence interval (CI):1.835–40.846, p = 0.006]. However, further extension of the treatment duration to 5 cycles was associated with a higher cumulative incidence of toxicities without additional efficacy benefits. Among patients with mutant NSCLC receiving ≥ 2 cycles of NTT followed by surgery, 4 cycles were associated with the highest observed MPR rate and acceptable safety. These observations provide preliminary evidence that 4 cycles may serve as a reference duration and warrant prospective validation.