Neoadjuvant and perioperative chemoimmunotherapy versus chemotherapy for resectable non-small-cell lung cancer: A...

Although neoadjuvant and perioperative chemoimmunotherapy improve outcomes in resectable non-small-cell lung cancer, treatment effects remain incompletely defined for specific subgroups. We searched PubMed, Embase, and Web of Science through 3 December 2025 and pooled eight randomized trials involving 3387 patients using random-effects models. Exploratory event-free survival (EFS) analyses yielded hazard ratios (HRs) of 0.57 for perioperative and 0.66 for pure neoadjuvant regimens versus chemotherapy. The indirect ratio of HRs was 0.86 (95% CI, 0.63-1.18; interaction P = 0.347), with insufficient precision to establish equivalence. Among patients with PD-L1 tumor-cell expression <1%, the pooled EFS HR was 0.77 (95% CI, 0.65-0.91), although all six trial-specific CIs included 1. China-only trials had numerically lower EFS HRs than international trials (0.48 versus 0.63; interaction P = 0.053). Surgery occurred in 82.2% versus 77.9% (risk ratio, 1.06; risk difference, 4.7 percentage points); nominal significance varied with study omission. Overall EFS and overall survival favored chemoimmunotherapy (HRs, 0.59 [95% CI,0.52-0.66] and 0.68 [0.57-0.80], respectively). Grade ≥3 treatment-related adverse events increased in the two eligible perioperative trials (risk ratio, 1.12; 95% CI, 1.02-1.24). Trial-level pathological response-survival analyses did not establish surrogate validity. Subgroup findings remain hypothesis-generating, and the surgical difference does not establish a clinically meaningful improvement in resectability.