Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis

Yixin Zhou,Xue Hou,Wenfeng Fang,Hongyun Zhao,Shaodong Hong,Sha Fu,Chen Chen,Yunpeng Yang,Cong Xue,Li Zhang,Xuanye Zhang,Yuxiang Ma,Yan Huang

doi:10.1186/s40425-018-0477-9

Abstract

BackgroundImmune-checkpoint inhibitors plus chemotherapy are emerging as effective first-line treatment in advanced non-small-cell lung carcinoma (NSCLC), but little is known about the magnitude of benefits and potential clinical predictors.MethodsWe performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy in first line of treatment for advanced NSCLC. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.ResultsSix trials involving 3144 patients were included. PD-1/PD-L1 inhibitor plus chemotherapy was significantly associated with improvement of PFS (hazards ratio [HR], 0.62; 95% CI 0.57–0.67; P < .001), OS (HR, 0.68; 95% CI 0.53–0.87; P = .002) and ORR (relative ratio [RR], 1.56; 95% CI 1.29–1.89; P < .001), irrespective of PD-L1 expression level. The significant predictor(s) for treatment benefit with combination therapy versus chemotherapy alone were PD-L1 expression level for PFS (P < .001); types of checkpoint inhibitor for ORR (P < .001); histology (P = .025), age (P = .038), gender (P < .001), and types of checkpoint inhibitor (P < .001) for OS. In safety analyses, PD-1/PD-L1 inhibitor plus chemotherapy had significantly higher incidence of adverse events (AEs) of grade 3 or higher (RR, 1.14; P = .007), AEs leading to treatment discontinuation (RR, 1.29; P = .022), serious AEs (RR 1.70; P = .006), immune mediated AEs of any grade (RR, 2.37; P < .001), and immune mediated AEs of grade 3 or higher (RR, 3.71; P < .001).ConclusionsPD-1/PD-L1 inhibitor plus chemotherapy, compared with chemotherapy, is associated with significantly improved PFS, ORR, and OS in first-line therapy in NSCLC, at the expense of increased treatment-related AEs.

Highlights

Immune-checkpoint inhibitors plus chemotherapy are emerging as effective first-line treatment in advanced non-small-cell lung carcinoma (NSCLC), but little is known about the magnitude of benefits and potential clinical predictors
The pooled estimates for progression-free survival (PFS) and overall survival (OS) were presented with Hazard ratio (HR), 95% Confidence interval (CI) and P values calculated using the inverse-variance-weighted method, while the measures for dichotomous data (ORR and frequency of adverse events) were pooled with the risk ratios (RRs), 95% CIs and P values using the Mantel Haenszel method
Subgroup analyses by PD-L1 expression level Programmed cell death 1 (PD-1)/PD-L1 inhibitor plus chemotherapy led to statistically longer PFS across all tested subgroups of PD-L1 expression level, including those with a PD-L1 tumor proportion score (TPS) of less than 1%

Summary

Methods

We performed a meta-analysis of randomized trials that compared PD-1/PD-L1 inhibitor plus chemotherapy with chemotherapy in first line of treatment for advanced NSCLC. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on between-study heterogeneity

Results

Conclusions

Background

Method

Discussion