PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

SIMPLE SUMMARY: Immunotherapy, particularly programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, has been responsible for changing the natural history of advanced or metastatic non-small cell lung cancer. However, its use in the resectable stage is not yet fully elucidated. Therefore, we aimed to evaluate the efficacy and safety of neoadjuvant and adjuvant use of PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone in resectable stage (I-III) non-small cell lung cancer. Our findings suggest that the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of non-small cell lung cancer. ABSTRACT: Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51–0.86) and event-free survival (HR 0.53; 95% CI 0.43–0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86–10.61) and pathological complete response (OR 8.82; 95% CI 4.51–17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69–0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.