PD-1/PD-L1 Antibody versus Gefitinib for Advanced Non-small Cell Lung Cancer: A Systematic Review and Network Meta-analysis of Randomized Control Trials
PD-1/PD-L1 antibody and gefitinib have made much progress in treatment of advanced non-small cell lung cancer. Recent randomized control trials revealed that both of them exhibited effective outcomes after first-line treatment, especially compared to chemotherapy. However, it is unknown that what’s the efficacy and safety between them due to lacking of direct evidences. Relevant randomized control trials were selected by searching electronic databases (PubMed, Embase, and Cochrane Library) and reference lists of related articles by hand. This study has been registered at International Prospective Register of Systematic Reviews (number CRD42018094297). According to Cochrane Handbook, two reviewers independently assessed eligibility and quality of the studies. The outcome measures were overall survival, progression-free survival, objective response rate and adverse events calculated through the fixed random effect model. PD-1/PD-L1 antibody could improve overall survival [HR=0.69(0.61-0.77), P=0.000] significantly over gefitinib, no matter of West Country, orient country and different PD-1/PD-L1 antibodies. While there was no significant difference between them in progression-free survival [HR=0.92(0.78-1.09), P=0.352] and objective response rate [HR=0.86(0.50-1.49), P=0.587]. Subgroup analysis suggested that PD-1/PD-L1 antibody could improve progression-free survival only for West Country [HR=0.83(0.71-0.96), P=0.010], and for objective response rate, similar results appeared only for orient country [HR=0.16(0.05-0.49), P=0.001] and atezolizumab [HR=0.50(0.27-0.94), P=0.031]. For incidence of adverse events, PD-1/PD-L1 antibody could reduce risk of nausea (all grades) [RR=0.65 (0.44-0.97), p=0.035], neutropenia (≥3 grade) [RR=0.30 (0.09-0.93), p=0.038], diarrhoea (all grades, ≥3 grade) [RR=0.26 (0.18-0.38), p=0.000, 0.23(0.08-0.67), p=0.007], rash (all grades) [RR=0.35 (0.14-0.84), p=0.019] and leukopenia (≥3 grade) [RR=0.19 (0.04-0.80), p=0.024] over gefitinib, but increase risk of fatigue (all grades) [RR=1.72 (1.18-2.49), p=0.004]. PD-1/PD-L1 monoclonal antibody is superior to gefitinib for overall survival for the after-first-line treatment of advanced NSCLC in general. Further considering survival and incidence of adverse events comprehensively, relative to gefitinib, PD-1/PD-L1 monoclonal antibody may be a better choice for advanced NSCLC.
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