Neoadjuvant Immunotherapy and Non-Small Cell Lung Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Objectives: To systematically evaluate the effectiveness and safety of neoadjuvant immunotherapy for patients with non-small cell lung cancer (NSCLC).

Methods: Randomized controlled trials of neoadjuvant immunotherapy in treating patients with NSCLC were comprehensively retrieved from electronic databases, eligible studies, previous systematic reviews and meta-analyses, guidelines, and conference abstracts. The meta-analysis was performed by the Stata/SE 12.0 software.

Results: Eleven randomized controlled trials were eventually included. The results of the meta-analysis showed that neoadjuvant immunochemotherapy significantly improved the objective response rate compared with neoadjuvant chemotherapy (CT; 62.46% vs 41.88%, P = 0.003), but the objective response rate of neoadjuvant double-immunotherapy was roughly comparable to that of neoadjuvant single-immunotherapy (15.74% vs 10.45%, P = 0.387). Major pathologic response (MPR) rate and pathologic complete response (pCR) rate of neoadjuvant immunochemotherapy and neoadjuvant double-immunotherapy were significantly superior to neoadjuvant CT alone and neoadjuvant single-immunotherapy, respectively. Compared with neoadjuvant CT alone, neoadjuvant immunochemotherapy increased the down-staging rate (40.16% vs 26.70%, P = 0.060), the surgical resection rate (83.69% vs 73.07%, P = 0.231), and R0 resection rate (86.19% vs 77.98%, P = 0.502), but there were no statistically significant differences. Neoadjuvant immunochemotherapy did not increase the postoperative complications rate than neoadjuvant CT alone (40.20% vs 41.30%, P = 0.920). In terms of safety, neoadjuvant immunochemotherapy and neoadjuvant double-immunotherapy did not increase the incidence of treatment-related adverse events (TRAEs) and the grade 3 or higher TRAEs.

Conclusions: In summary, neoadjuvant immunochemotherapy had better clinical efficacy than neoadjuvant CT for patients with NSCLC. MPR rate and pCR rate of neoadjuvant immunochemotherapy and neoadjuvant double-immunotherapy were significantly superior to neoadjuvant CT and neoadjuvant single-immunotherapy, respectively, for patients with NSCLC, showing that MPR rate and pCR rate were probably considered as alternative endpoints for survival benefit. TRAEs were comparable between the corresponding groups. The long-term survival outcome of neoadjuvant immunotherapy for patients with NSCLC needs to be further confirmed to better guide clinical practice.

FIGURE 1

“Preferred Reporting Items for Systematic Reviews and Meta-analyses” flow diagram of the selection process of the studies included in the systematic review and meta-analysis.

FIGURE 2

Begg funnel plot for the publication bias test.