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Efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer.

ABSTRACT: Immune checkpoint inhibitors (ICIs) are new therapeutic strategies for non-small cell lung cancer (NSCLC). We aimed to quantitatively evaluate the efficacy and safety of ICIs in NSCLC. Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized clinical trials comparing ICIs with control therapies in NSCLC. Data were pooled according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A total of 12 trails comprising 6,919 NSCLC patients were included in this meta-analysis. ICIs therapies significantly improved progression-free survival (PFS) (HR, 0.838; P < 0.001), overall survival (OS) (HR, 0.747; P < 0.001) and objective response rates (ORR) (RR, 1.311; P < 0.001) in NSCLC. Prognostic benefit was observed irrespective of age, sex, treatment line, performance status and histology. Survival improvement of ICIs was limited for NSCLC patients with non-smoker (PFS, P = 0.468; OS, P = 0.317) or central nervous system (CNS) metastasis (PFS, P = 0.209; OS, P = 0.090), or positive EGFR mutation (PFS, P = 0.083; OS, P = 0.522) or PD-L1 expression level less than 5% (PFS, P = 0.370; OS, P = 0.047). The relative risks of all-grade and high-grade (≥3) anemia, neutropenia, leukopenia, thrombocytopenia, stomatitis, nausea, pyrexia, asthenia and neuropathy were all decreased in patients received ICIs compared with control therapies. This meta-analysis provides clinical evidence that ICIs improve PFS, OS, and ORR in NSCLC with fewer adverse effects. Our data establish ICIs as a prefer treatment option for NSCLC patients with smoker, no CNS metastasis, wild type EGFR, and high PD-L1 expression.

SUBMITTER: Wang S

PROVIDER: S-EPMC6136858 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer.

Wang Shuai S Hao Jiatao J Wang Hao H Fang Yong Y Tan Lijie L

Oncoimmunology 20180424 8

Immune checkpoint inhibitors (ICIs) are new therapeutic strategies for non-small cell lung cancer (NSCLC). We aimed to quantitatively evaluate the efficacy and safety of ICIs in NSCLC. Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized clinical trials comparing ICIs with control therapies in NSCLC. Data were pooled according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A total of 12 trails comprising 6,919 NSCLC patients were in ...[more]

PMID: 30221052

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Project description:BackgroundTherapeutic strategies with immune checkpoint inhibitors (ICIs) counteract the immunosuppressive effects of programmed cell death protein-1 (PD-1) and ligand-1 (PD-L1). ICI treatment has emerged in first- and second-line therapy of non-small cell lung cancer (NSCLC). As immunotherapeutic treatment with ICIs is a dynamic field where new drugs and combinations are constantly evaluated, we conducted an up-to-date systematic review on comparative efficacy and safety in patients with advanced NSCLC.MethodsWe searched PubMed up to February 2020 and Embase, CENTRAL, and clinical trial registries up to August 2018. Additionally, we checked reference lists. We dually screened titles, abstracts and, subsequently, full-texts for eligibility. Two reviewers assessed the risk of bias and graded the certainty of evidence following GRADE (Grading of Recommendations Assessment, Development and Evaluation). For second-line therapy, we performed random-effects meta-analyses. Due to considerable clinical heterogeneity, we reported first-line results narratively.ResultsOf 1497 references, we identified 22 relevant publications of 16 studies. For first-line therapy, a combination of an ICI with chemotherapy improved progression-free survival and overall survival compared to chemotherapy but increased the risk of serious adverse events. Single-agent pembrolizumab increased overall and progression-free survival in patients with PD-L1 expression of ≥50% and resulted in less TRAE than chemotherapy. Compared to placebo, maintenance therapy with durvalumab increased overall and progression-free survival at the downside of higher risk of TRAE. For second-line therapy, a random-effects meta-analysis yielded a statistically significantly improved overall survival (OS) and progression-free survival (PFS) for ICIs compared to docetaxel (HR 0.69; 95% CI: 0.63-0.75 for OS; HR 0.85; 95% CI: 0.77 - 0.93 for PFS; 6 studies, 3478 patients; median OS benefit in months: 2.4 to 4.2). In meta-analysis, risk of any treatment-related adverse events of any grade was lower for ICI than docetaxel as second-line therapy (RR 0.76, 95% CI: 0.73-0.79; 6 studies, 3763 patients).ConclusionIn first-line therapy of patients with advanced NSCLC, ICI is effective when combined with chemotherapy not depending on PD-L1 expression, or as monotherapy in high PD-L1 expressing tumors. For second-line therapy, single-agent ICI improves efficacy and safety compared to docetaxel.

Dataset Information

Efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer.

Publications

Efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer.

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