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

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.