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. 2019 Feb 18:11:1623-1629.
doi: 10.2147/CMAR.S188551. eCollection 2019.

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

Jie Li  1 , Qi He  1 , Xiu Yu  1 , Khalid Khan  1 , Xuanwen Weng  1 , Minjie Guan  1
Affiliations

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

Jie Li et al. Cancer Manag Res. .

Abstract

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.

Keywords: complete response; immune checkpoint inhibitors; immunotherapy therapy; meta-analysis; non-small-cell lung cancer; randomized controlled trials; systematic review.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Selection process of RCTs included in the meta-analysis. Abbreviations: CR, complete response; ICIs, immune checkpoint inhibitors; RCT, randomized controlled trial.
Figure 2
Figure 2
Subgroup analysis based on treatment line for RR of CR associated with ICIs vs CT. Abbreviations: CR, complete response; CT, chemotherapy; ICI, immune checkpoint inhibitor; NA, not available.
Figure 3
Figure 3
Correlation between median OS and PFS in NSCLC patients who received ICIs. Abbreviations: ICI, immune checkpoint inhibitor; NSCLC, non-small-cell lung cancer; OS, overall survival; PFS, progression-free survival.
Figure 4
Figure 4
Correlation between median OS and CR in NSCLC patients who received ICIs. Abbreviations: CR, complete response; ICI, immune checkpoint inhibitor; NSCLC, non-small-cell lung cancer; OS, overall survival.
Figure 5
Figure 5
Correlation between median OS and ORR in NSCLC patients who received ICIs. Abbreviations: ICI, immune checkpoint inhibitor; NSCLC, non-small-cell lung cancer; ORR, objective response rate; OS, overall survival.
See this image and copyright information in PMC

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