Complete response associated with immune checkpoint inhibitors in advanced non-small-cell lung cancer: a meta-analysis of nine randomized controlled trials

Purpose: The purposes of this study were to investigate whether the use of immune checkpoint inhibitors (ICIs) in advanced non-small-cell lung cancer (NSCLC) would increase the possibility of archiving complete response (CR) and assess the surrogate end points for overall survival (OS). Methods: We calculated the incidence and relative risk (RR) of CR events in patients assigned to ICIs compared to that in controls. Simple linear regression models were fitted for median OS and each surrogate (median progression-free survival [PFS], CRs, and objective response rate [ORR]). Results: A total of 4,803 NSCLC patients from nine randomized controlled trials (RCTs) were included for analysis. The incidence of CR in NSCLC patients treated with ICIs was 1.5% (95% CI: 0.8-3.0) compared to 0.7% (95% CI: 0.4-1.2) in chemotherapy (CT) groups. The use of ICIs in advanced NSCLC significantly improved the possibility of archiving CR (RR 2.89, 95% CI: 1.44-5.81, P=0.003) compared to CT. Subgroup analysis according to ICIs showed that the use of atezolizumab (RR 3.26, P=0.01) and nivolumab (RR 4.83, P=0.042) in advanced NSCLC significantly improved the CR rate in comparison with CT alone, but not pembrolizumab and ipilimumab. We also found that the use of ICIs as first-line (RR 2.39, 95% CI: 1.08-5.3, P=0.032) or second-line (RR 4.99, 95% CI: 1.10-22.66, P=0.038) therapy significantly increased the change in obtaining a CR. In addition, correlation analysis indicates that PFS was strongly correlated with OS in NSCLC patients who received ICIs (r=0.89 for PFS, P=0.017). No marked correlation was found between OS and CR (r=0.19, P=0.75) and OS and ORR (r=0.52, P=0.28). Conclusion: The CR is a rate event in advanced NSCLC, but the use of ICIs significantly increases the possibility of archiving CR in comparison with CT. PFS is significantly correlated with OS and could be used as a surrogate end point, but not for CRs and ORRs.