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    Checkpoint inhibitors in advanced nonsmall-cell lung cancer; a Bayesian network meta-analysis
    (Wolters Kluwer Medknow Publications, 2020) Bozcuk, Hakan; Yildirim, Mustafa; Sever, Ozlem; Mutlu, Hasan; Artac, Mehmet
    Background: Checkpoint inhibitors (CPIs) have improved survival compared to chemotherapy alone in advanced nonsmall-cell lung cancer (NSCLC). This article aims to compare indirect evidence and rank the effect of different CPIs in this setting. Materials and Methods: In this network meta-analysis, we searched for trials comparing CPIs in advanced NSCLC. Figures for survival endpoints were extracted. In addition, a network meta-regression analysis was carried out. Results: A total of 9220 patients from 16 trials were included in the analysis. In the first-line setting, for the overall survival endpoint, the chemotherapy + Pembrolizumab combination had the highest effectivity rank probability as compared to chemotherapy (hazard ratio = 0.788, 95% credential interval = 0.728-0.855). For the second-line setting, and also for the efficacy in terms of progression-free survival, various CPIs and their combinations were ranked. Conclusion: Some degree of differences in terms of efficacy exists between different types, dosages, settings, and combinations of CPI. We quantify these differences to guide clinical practice.
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    Programmed death-1 or programmed death ligand-1 inhibitors? A meta-analysis of differential efficacy as compared to chemotherapy in advanced non-small cell lung cancer
    (Sage Publications Ltd, 2021) Bozcuk, Hakan; Artac, Mehmet; Mutlu, Hasan; Sever, Ozlem; Yildirim, Mustafa
    Background Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PDL-1) inhibitors have improved survival over chemotherapy in advanced Non- Small Cell Lung Cancer (NSCLC). However, it is unclear if there are class specific differences in the efficacy of Checkpoint Inhibitors (CPIs) in NSCLC, and this paper is designed to answer these clinical questions. Methods For this Meta-analysis, we searched PubMed, Science of Web, Clinicaltrials.gov and online sources for trials comparing PD-1 and PDL-1 CPIs in advanced NSCLC. The data for Hazard Ratio (HR) and their Confidence Intervals (CI) for Overall Survival (OS) was extracted. Results A sum of 9739 patients from 16 trials were included in the efficacy evaluation. For the OS endpoint, both PD-1 inhibitors (HR = 0.76, 95%CI = 0.69-0.83, P < 0.001) and PDL-1 inhibitors (HR = 0.84, 95%CI = 0.74-0.95, P < 0.001) were superior to chemotherapy in treatment naive (upfront) patients, the results were similar in treatment refractory patients (PD-1 inhibitors (HR = 0.67, 95%CI = 0.60-0.75, P < 0.001) and PDL-1 inhibitors (HR = 0.78, 95%CI = 0.69-0.88, P < 0.001) were superior to chemotherapy). There was no difference in the effect of PD-1 and PDL-1 classes of CPIs over chemotherapy in treatment naive and treatment refractory settings (Q = 1.88, df = 1, P = 0.017, and, Q = 3.27, df = 1, P = 0.070, respectively). Conclusion Efficacy of PD-1 and PDL-1 class of CPIs was not different, although differences among individual CPIs or their combinations cannot be excluded. We were also able to compute pooled efficacy data, as compared to chemotherapy alone, for trials where these groups of CPIs were utilized.