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First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis.

ABSTRACT: Background:The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting. Methods:The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a pre-specified search strategy. Searches were conducted using PubMed, Medline, and EMBASE, with supplemental searches using the Evidence Based Medicine Reviews and ClinicalTrials.gov to identify RCTs published in English from 1995-2016 and reporting at least one of the primary outcomes [overall survival (OS), progression-free survival (PFS), toxicity, or quality of life] in patients who received first-line treatment for advanced or metastatic squamous NSCLC. Study quality and risk of bias were assessed using the Physiotherapy Evidence Database (PEDro) scale and Cochrane risk of bias tool, respectively. A Baysian network meta-analysis was performed on the primary outcomes. Hazard ratios (HRs) were evaluated for the primary analysis; secondary analyses were conducted using median OS data. Planned sensitivity analyses were conducted including reanalysis using a Frequentist approach and limiting analyses to subsets based on clinical and demographic covariates. Results:The systematic literature review resulted in identification of 4,016 unique publications; 40 publications (35 unique trials) were eligible for inclusion. Eight studies connected to a common network for the OS analysis using HR data. The majority of studies were not limited to squamous NSCLC, thus analyzable data were limited to a subset of data within the published trials. Carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin were associated with lower HRs for OS versus all other comparators. Nine studies connected to the network for the PFS analysis in which necitumumab in combination with gemcitabine and cisplatin was associated with the lowest HR. Data were not available to analyze toxicity or quality of life. Conclusions:Although the results suggest that carboplatin + S-1 and necitumumab in combination with gemcitabine and cisplatin may have value in terms of OS versus other comparators, the results should be interpreted with caution due to the limited number of studies (with few focused exclusively on squamous NSCLC) and wide credible intervals.

SUBMITTER: Hess LM

PROVIDER: S-EPMC6344765 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis.

Hess Lisa M LM DeLozier Amy M AM Natanegara Fanni F Wang Xiaofei X Soldatenkova Victoria V Brnabic Alan A Able Stephen L SL Brown Jacqueline J

Journal of thoracic disease 20181201 12

<h4>Background</h4>The objectives of this systematic review and meta-analysis were to compare the survival, toxicity, and quality of life of patients treated with necitumumab in combination with gemcitabine and cisplatin. These agents were investigated in published randomized controlled trials (RCTs) of patients with squamous non-small cell lung cancer (NSCLC) in the first-line setting.<h4>Methods</h4>The systematic review was executed on January 27, 2015, and updated on August 21, 2016, using a ...[more]

PMID: 30746213

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Project description:IntroductionClinical evidence suggests that first-line immune checkpoint inhibitor (ICI) combination therapies can improve survival in patients with advanced non-squamous non-small cell lung cancer (nsq-NSCLC). However, the optimal strategy remains unknown without a systematic comparison of their long-term effects.MethodsWe performed a systematic review and network meta-analysis by retrieving up-to-date literature from PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, Netherlands), MEDLINE® (National Library of Medicine), ClinicalTrials.gov (National Library of Medicine), and major international conference publications. Published studies and abstracts comparing first-line ICI combination therapies with other treatments for patients with advanced nsq-NSCLC were included. Restricted mean survival time (RMST) was measured over 12 months for progression-free survival (PFS) and 18 months for overall survival (OS), and the Royston-Parmar model was used to extrapolate and compare data for the long-term outcomes.ResultsWe included a total of 11 trials involving 12 therapies and 6,130 patients. Pembrolizumab plus chemotherapy exhibited the best overall survival (OS) benefit at both 18 and 60 months [RMST = 2.95, 95% confidence interval (CI) 1.96 to 3.97; life-years gained over a 5-year period = 2.18 years]. Nivolumab plus bevacizumab plus chemotherapy was found to present the best progression-free survival (PFS) benefit at 12 months (RMST 3.02, 95% CI 2.11 to 3.91), whereas atezolizumab plus bevacizumab plus chemotherapy showed the best PFS benefit at 36 months (life-years gained over 3 years = 1.22 years). Subgroup analyses showed that among patients with programmed death-ligand 1 (PD-L1) expression ≥ 50%, atezolizumab plus chemotherapy and nivolumab plus ipilimumab resulted in superior OS benefits at 18 and 60 months, respectively. Among patients with PD-L1 expression< 1%, pembrolizumab plus chemotherapy was associated with OS benefits at both 18 and 60 months. Sintilimab plus chemotherapy was associated with relatively fewer grade ≥ 3 adverse events than other ICI combination therapies.ConclusionOur results show that ICI combination therapies showed better survival benefits than chemotherapy. Pembrolizumab plus chemotherapy could provide the best OS benefits to patients with advanced nsq-NSCLC, whereas atezolizumab plus bevacizumab plus chemotherapy could bring the best PFS benefits. The optimal ICI combination therapy varies depending on PD-L1 expression level.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=325005, identifier CRD42022325005.

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First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis.

Publications

First-line treatment of patients with advanced or metastatic squamous non-small cell lung cancer: systematic review and network meta-analysis.

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