Checkpoint Inhibitors in the First-Line Setting in Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

Abstract

Background: While the standard first-line therapy for patients with advanced Non-Small-Cell Lung Cancer (NSCLC) without targetable genetic aberrations is platinum-based chemotherapy (CTX), recently, inhibitors of Programmed Cell Death-1 (PD-1) or its Legend (PD-L1) have set a novel option for such patients. To quantify the overall efficacy of those agents here Called Checkpoint Inhibitors (CPIs) and in patient subgroups, this meta-analysis was performed. Methods: Using a defined selection criterion, a literature search identified 12 Randomized Clinical Trials (RCTs) involving 7,095 patients where CPIs have been used in the first-line setting. Results: In five RCTs, CPIs were compared against CTX, a comparable progression-free survival was observed (hazard ratio [HR] = 0.88; 95% CI, 0.77-1.01; P = 0.06), with a significant 21% decreased in mortality (HR = 0.79 (95% CI, 0.71-0.87); P = <0.0001). Improved overall survival was attained across all relevant patient subgroups. In the remaining seven RCTs examining CPIs plus CTX versus CTX alone, the combined regimens reduced progression and deaths by 39% (HR = 0.61; 95% CI 0.57-0.66; P <0.0001), and 26% (HR = 0.74; 95% CI, 0.630.88; P <0.0001), respectively. CPIs plus CTX versus CTX alone doubled the objective response rate. Patients with high PD-L1 expression consistently achieved the highest benefit, although some patients with low expression have also benefited. Number of patients in included studies, male gender proportion, PD-L1 expression, and median duration of follow-up were the variables that explained heterogeneity in the pooled outcome. Conclusion: Current evidence indicates significant efficacy with the use of CPIs mostly in combination with CTX as the first-line therapy in NSCLC without targetable agents. Besides the levels of PD-L1 expression, identifying additional predicting biomarkers is needed. Citation: Ibrahim EM, Refae AA, Bayer AM, Al-Masri OA, Eldahna WM, et al. Checkpoint Inhibitors in the First-Line Setting in Advanced Non-Small Cell Lung Cancer: A Meta-AnalysisJ Cancer Sci. 2019;6(1): 14. J Cancer Sci 6(1): 4 (2019) Page 02 ISSN: 2377-9292 Materials and Methods