Immune checkpoint inhibitors as neoadjuvant therapy for resectable non-small cell lung cancer: a systematic review and network meta-analysis

Immune checkpoint inhibitor (ICI) has improved survival outcomes in patients with resectable non-small cell lung cancer (NSCLC). Recent clinical trials have evaluated several ICI strategies including neoadjuvant-only chemoimmunotherapy, neoadjuvant-adjuvant (perioperative) chemoimmunotherapy, adjuvant-only chemoimmunotherapy, and ICI single- and dual-therapy. However, the optimal perioperative approach remains unclear. As a systematic review, databases were searched to identify eligible randomized controlled trials (RCTs) evaluating perioperative treatment incorporating at least one ICI as perioperative therapy for resectable NSCLC. A random model network meta-analysis was performed. All statistical tests were two-sided. Eleven RCTs with 4,532 patients were included in the analysis. Seven perioperative strategies were compared; however, some were not comparable due to the presence of independent loops. The addition of adjuvant ICI therapy to neoadjuvant chemoimmunotherapy was not associated with improved event-free survival (EFS) (Hazard Ratio HR 0.97, 95% confidence interval 95% CI 0.67-1.41, p = .87) or overall survival (HR 1.17, 95% CI 0.59-2.31, p = .65). When comparing adjuvant-only chemoimmunotherapy to neoadjuvant-only and perioperative chemoimmunotherapy, both neoadjuvant-only and perioperative strategies showed numerically longer OS compared to adjuvant-only chemoimmunotherapy, although the differences were not statistically significant. Regarding safety, the addition of ICI treatment to neoadjuvant chemoimmunotherapy did not significantly increase the incidence of any-grade, grade 3-5, or grade 5 TRAEs. No clear benefit was observed for adding adjuvant ICI therapy to neoadjuvant chemoimmunotherapy. Further research is needed to directly compare neoadjuvant-only vs perioperative chemoimmunotherapy, and to determine the optimal number of cycles and duration of ICI treatment for patients with resectable NSCLC.