Checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced squamous non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

Abstract

121 Background: Squamous Non-small cell lung cancer (NSCLC) accounts for ~30% of lung cancers, and long-term survival remains poor for advanced disease. Combined chemo-immunotherapy can have synergistic anticancer activities through the immunomodulatory impact of checkpoint inhibitors and the immunogenic effect of chemotherapy. Methods: We systematically conducted a comprehensive literature search using PUBMED, EMBASE and SCOPUS databases through October 1, 2018. RCTs of first-line chemotherapy +/- immunotherapy in patients with advanced squamous NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). The mantel-haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI) for pooled overall response rate (ORR), all-grade adverse events (AEs), and high-grade AEs (≥grade 3). Heterogeneity was assessed with Cochrane Q -statistic. Random effects were used due to significant heterogeneity among studies. Results: Three phase 3 RCTs (Keynote – 407, IMpower – 131, and Govindan et al) including 1991 patients with advanced squamous NSCLC patients were included in the meta-analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, or atezolizumab, while control arm used only standard chemotherapy regimens. The pooled HR for PFS was 0.71 (95% CI: 0.56-0.9; P = 0.005), the pooled HR for OS was 0.84 (95% CI: 0.68-1.04; P = 0.11), and the pooled RR for ORR was 1.19 (95 CI: 0.9-1.56; P = 0.22). The pooled RRs for all-grade AEs and high-grade AEs were 1.17 (95% CI: 0.99-1.39; P = 0.07) and 1.36 (95% CI: 1.19-1.56; P = 0.0001), respectively. Conclusions: The combined chemo-immunotherapy improves PFS without significant improvement in OS & ORR compared to standard chemotherapy for the first-line treatment of advanced squamous NSCLC. The combined regimen results in a slightly higher risk of high-grade AEs without a significant increase in the risk of all-grade AEs.