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.