Efficacy of checkpoint inhibitors, tumor vaccines, and cellular immunotherapies in patients with advanced non-small cell lung cancer.

Abstract

165 Background: Checkpoint inhibitors, tumor vaccines or cellular immunotherapies demonstrated prolonged survival versus placebo or observation in several randomized clinical trials (RCTs) of patients with advanced non-small-cell lung cancer (NSCLC). We aimed to clarify the benefits of imunotherapy by a meta-analysis of RCTs data. Methods: We searched for RCTs investigating immunotherapy versus placebo or observation in patients with advanced NSCLC. Overall survival (OS) and progression-free survival (PFS) were calculated as combined hazard ratios (HRs). The quality of the evidence was evaluated with the GRADE framework. Results: Overall, 23 RCTs including a total of 8,956 patients were identified (5,142 patients in the immunotherapy group and 3,814 in the placebo or observation group). High- to moderate-quality evidence indicated that immunotherapy prolonged OS (HR = 0.79, 95% confidence interval (CI) 0.75 to 0.84, P < 0.0001) and PFS (HR = 0.80, 95% CI 0.73 to 0.88, P < 0.0001). In subgroup analysis, high- to moderate-quality evidence revealed immunotherapy extended NSCLC survival and PFS in tumor vaccines (HR, 0.84, 95% CI 0.76 to 0.92 and 0.86, 95% CI 0.78 to 0.94 for OS and PFS, respectively), checkpoint inhibitors (0.77, 95% CI 0.72 to 0.83 and 0.78, 95% CI 0.68 to 0.90, respectively), maintenance therapy (0.77, 95% CI 0.71 to 0.83 and 0.78, 95% CI 0.66 to 0.91, respectively), first-line therapy (0.89, 95% CI 0.80 to 0.98 and 0.76, 95% CI 0.64 to 0.91, respectively), previous definitive chemotherapy (0.72, 95% CI 0.67 to 0.78 and 0.87, 95% CI 0.79 to 0.95, respectively), and concurrent chemotherapy (0.87, 95% CI 0.80 to 0.95 and 0.84, 95% CI 0.77 to 0.91, respectively). There was a benefit of immunotherapy in previous definitive chemotherapy compared with chemoradiotherapy and with concurrent administration of chemotherapy (OS as HR: P = 0.002 and P = 0.006, respectively). Conclusions: This analysis provides strong evidence for OS and PFS benefit of immunotherapy in patients with advanced NSCLC, particularly in those receiving tumor vaccines, checkpoint inhibitors, maintenance and first-line therapy, previous definitive chemotherapy, and with concurrent chemotherapy.