Short-term outcome of neoadjuvant immunotherapy and chemotherapy in non-small cell lung cancer: A systematic review and meta-analysis

Background: Previously reported results have shown promising efficacy fi cacy of neoadjuvant immunotherapy for resectable non-small - small cell lung cancer (NSCLC). However, no randomized control trials comparing neoadjuvant immunotherapy with chemotherapy have yet been reported. The aim of the present study was to evaluate the superiority of neoadjuvant immunotherapy compared with standard neoadjuvant chemotherapy in resectable NSCLC in terms of short-term clinical outcomes and surgical outcomes. Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov database, Web of Science, and abstracts derived from multiple major cancer meetings up to March 1, 2020. Short-term clinical outcomes (including objective response rate [ORR], major pathologic response, and pathologic complete response [pCR]) and surgical outcomes (including surgical resection rate and R0 resection rate) were reported. Data were summarized as the estimated pooled value of each evaluated index. The risk of bias of included studies was assessed using standard methods. Results: This systematic review and meta-analysis of 21 trials on neoadjuvant immunotherapy and neoadjuvant chemotherapy for NSCLC included 1795 patients. Patients who received Programmed death ligand 1 (PD-1/PD-L1) inhibitors (NeoIO) alone (13.3%; % ; 95% % confidence fi dence interval [CI], 9.0%-19.3%) %-19.3 % ) had the lowest ORR compared with those who received NeoIO plus chemotherapy (CT) (62.5%; % ; 95% % CI, 54.4%-70.0%) %-70.0 % ) or CT alone (41.6%; % ; 95% % CI, 36.8%-46.7%) %-46.7 % ) (NeoIO vs CT, P < .001; NeoIO + CT vs CT, P < .001). Receipt of NeoIO + CT (36.2%; % ; 95% % CI, 19.2%-57.6%) %-57.6 % ) was associated with an elevated pCR rate compared with receipt of NeoIO alone (10.6%; % ; 95% % CI, 6.5%-16.9%; %-16.9 % ; P < .001) or standard CT (7.5%; % ; 95% % CI, 5.7%-9.8%; %-9.8 % ; P < .001). Neoadjuvant CT (87.2%; % ; 95% % CI, 74.9%- %- 94.0%) % ) was associated with a lower R0 resection rate compared with NeoIO alone (92.7%; % ; 95% % CI, 83.4%-97.0%; %-97.0 % ; P = .360) or NeoIO + CT (91.6%; % ; 95% % CI, 84.3%- %- 95.7%; % ; P = .409). Meta-regression showed that a higher proportion of stage III patients was correlated with decreased surgical resection and R0 resection rates, whereas no impact was observed with neoadjuvant immunotherapy. Conclusions: Current data suggest that compared with neoadjuvant chemotherapy, immunotherapy-based regimens may provide superior pathological response along with a higher rate of complete resection. Immunotherapy combined with chemotherapy in neoadjuvant chemotherapy may be a more favorable clinical option. Further randomized controlled trials are warranted to provide long-term results of neoadjuvant immunotherapy for localized NSCLC and help guide clinical practice. (JTCVS Open 2021;8:588-607)