Network meta-analysis of perioperative immunotherapies in non-small-cell lung cancer according to tumor programmed death ligand 1 expression.

Objective: Immunotherapy has emerged as a therapeutic alternative to chemotherapy (CT) for perioperative treatment of resectable non-small cell lung cancer (NSCLC). The objective is to perform a network meta-analysis comparing the perioperative efficacy of immunotherapies in resectable NSCLC taking into account tumor expression of programmed death ligand 1 (PD-L1).

Method: A review was performed in Pubmed® and EMBASE® until September 17, 2024. Phase III clinical trials on perioperative immunotherapies (P-) for resectable NSCLC with ≥50 patients were included. The selected endpoint was progression-free survival (PFS) according to different levels of PD-L1 expression. The statistical analysis used Bayesian methods. Fixed- or random-effects models were assessed using deviance information criteria (DIC). A sensitivity analysis was developed to evaluate the influence of heterogeneous studies.

Results: Four trials were included. Immunotherapeutic schemes with P-toripalimab, P-nivolumab, P-pembrolizumab and P-durvalumab were selected. Only P-toripalimab included a cycle of adjuvant toripalimab + CT. The remaining perioperative combinations contained the neoadjuvant immunotherapeutic agent + CT (4 cycles) regimen followed by adjuvant immunotherapy. The common comparator was neoadjuvant placebo + CT with adjuvant placebo (P-placebo). P-toripalimab was evaluated in a population with heterogeneous characteristics. Fixed effects model was selected for DIC values with irrelevant differences. P-toripalimab obtained greater magnitude of effect in PFS for populations with PD-L1 < 1% and 1-49% (reference treatment). No benefit of any immunotherapeutic combination over P-placebo was observed in resectable NSCLC with PD-L1 expression <1%. P-toripalimab was statistically superior to the other regimens [except P-pembrolizumab, HR = 1.6 (95%CrI: 0.84-3.2)] for PD-L1 expression 1-49%. Immunotherapeutic schemes were superior to p-placebo for PD-L1 expression ≥50%. Sensitivity analysis showed results compatible with the primary analysis.

Conclusions: Our network meta-analysis provides reliable evidence on the efficacy of perioperative immunotherapy in resectable NSCLC according to PD-L1 expression levels, and may favor competition between therapeutic alternatives. A sensitivity analysis supported these results.