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• W2898096006 abstract "Checkpoint inhibitors targeting the programmed death-1 (PD-1)/PD-ligand 1 (L1) pathway have become a standard treatment in advanced non-small cell lung cancer (NSCLC) in the first and second line setting. Yet, subgroup analyses from randomized trials have shown inconsistent results regarding survival benefit in elderly patients (> 65 years old), never-smokers and patients with PD-L1 (-) expressing tumors (<1%). We conducted a systematic review and meta-analysis to assess the efficacy of checkpoint inhibitors in these pre-defined subgroups of patients. The electronic databases PubMed and EMBASE, were searched for relevant randomized trials between January 2005 and December 2017. Pooled hazard ratios (HR) for overall survival (OS) and progression free survival (PFS) were meta-analyzed using the generic inverse variance method. To account for between-studies heterogeneity, random-effect models were used to compute pooled estimates. Subgroup analyses compared patients treated in the first versus second line setting. Seven studies were included. Compared to chemotherapy, a significant reduction in the risk of death was seen with the use of checkpoint inhibitors in the second line independent of PD-L1 expression (4 studies, 2,364 participants, HR=0.79, 95%CI 0.66-0.96 and HR=0.66, 95%CI 0.57-0.78 in PD-L1 (–) and (+) patients respectively). Yet, a PFS benefit was only seen in patients with PD-L1 (+) tumors (2 studies, 852 participants, HR=0.69, 95%CI 0.55-0.88). Similarly, an OS benefit was seen in patients independent of age (5 studies, 3,651 participants, HR=0.77, 95%CI 0.64-0.92 and HR=0.75, 95%CI 0.6-0.94 in elderly and non-elderly patients respectively). Conversely, an OS benefit was only seen in ever-smokers (5 studies, 2,905 participants, HR=0.76, 95%CI 0.63-0.92 in ever-smokers and HR=0.83, 95%CI 0.64-1.08 in never-smokers) and a detrimental effect on PFS in never-smokers (3 studies, 1,426 participants, HR=1.68, 95%CI 1.07-2.63). In subgroup analyses, with the use of checkpoint inhibitors, elderly patients derived an OS benefit only in the second line setting (HR=0.69, 95%CI 0.59-0.81). Furthermore, never-smokers had no OS benefit in the first or second line (HR=1.02, 95%CI 0.54-1.93 and HR=0.79, 95%CI 0.59-1.07 respectively) and worse PFS particularly in the first line (HR=2.3, 95%CI 1.23-4.3). In the second line setting, patients with advanced NSCLC derive a survival benefit from checkpoint inhibitors independent of tumor PD-L1 expression and age. However, never-smokers do not benefit from these drugs particularly in the first line. Caution should be exercised when offering checkpoint inhibitors to elderly patients with advanced NSCLC in the first line and further research is needed to define their role in never-smokers." @default.
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• W2898096006 date "2018-10-01" @default.
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• W2898096006 title "P3.04-19 Do Advanced Lung Cancer Patients Derive Similar Survival Benefits from Immunotherapy? A Systematic Review and Meta-Analysis" @default.
• W2898096006 doi "https://doi.org/10.1016/j.jtho.2018.08.1726" @default.
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