Efficacy and safety of anti-PD-1/PD-L1 in combination with chemotherapy or not as first-line treatment for advanced non-small cell lung cancer: A systematic review and network meta-analysis

Background The aim of this network meta-analysis (NMA) was to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors, alone or in combination with chemotherapy, as first-line treatment for wild-type advanced non-small cell lung cancer. Methods We systematically searched databases, Clinical Trial.gov and included randomized clinical trials focusing on advanced NSCLC using PD-1/PD-L1 inhibitors as first-line treatment. Hazard ratio for overall survival and progression-free survival, odds ratio for any-cause high-adverse events (grade 3 or higher) were documented according to Bayesian NMA. Subgroup analysis was performed according to PD-L1 level and histology. Results Thirteen trials including 9154 patients were included. In the PD-L1 nonselective cohort, chemotherapy in combination with pembrolizumab and atezolizumab, respectively, were significantly better than any other treatment strategies in both OS benefit (HR = 0.63; HR = 0.85) and PFS benefit (HR = 0.52; HR = 0.63). In subgroup analysis, pembrolizumab appeared to provide the best OS benefit (HR = 0.67) as well as the best PFS benefit (HR = 0.67) in the PD-L1 >= 50% cohort. In contrast, pembrolizumab combined with chemotherapy exhibited the best OS benefit in the PD-L1 < 50% cohort. Furthermore, OS benefit from pembrolizumab plus chemotherapy was more obvious in nonsquamous patients (HR = 0.56). Additionally, pembrolizumab plus chemotherapy was associated with fewer adverse events than other chemotherapy combination strategies. Conclusions In the first-line treatment, chemotherapy plus pembrolizumab or atezolizumab could enhance efficacy compared with chemotherapy alone or other PD-1/L1-based treatment strategies, especially in the nonsquamous population. Furthermore, pembrolizumab plus chemotherapy guarantees reliable security simultaneously, which may be the optimal treatment strategy for patients with major advanced NSCLC.