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

    Research output: Contribution to journalReview article

    19 Scopus citations

    Abstract

    Background: 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. 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: Six 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). Conclusions: PD-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.

    Original languageEnglish (US)
    Article number155
    JournalJournal for immunotherapy of cancer
    Volume6
    Issue number1
    DOIs
    StatePublished - Dec 22 2018

    Keywords

    • Chemotherapy
    • Immune checkpoint inhibitor
    • Non-small cell lung carcinoma
    • Predict
    • Programmed death 1
    • Programmed death 1 ligand 1

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Molecular Medicine
    • Oncology
    • Pharmacology
    • Cancer Research

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