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

Abstract

Background Atezolizumab, an ani-PD-L1 monoclonal antibody, has been used in the treatment of a wide variety of cancers. Recently, atezolizumab has shown significant antitumor activity against non-small cell lung cancer (NSCLC), the majority of lung cancer which is the leading cause of cancer-related mortality in both sexes. The purpose of our study is to consolidate the efficacy of atezolizumab in combination with chemotherapy for first-line treatment of advanced NSCLC. Methods We systematically conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs utilizing first-line atezolizumab chemoimmunotherapy in patients with advanced NSCLC were incorporated. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q -statistic. Random effects model was applied. Results A total of 2725 patients with advanced NSCLC from four phase III RCTs (IMpower – 130, 131, 132 and 150) were eligible. The study arm used standard chemotherapy regimens in combination with atezolizumab while control arm used only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower130 study and 1:1 in other studies. IMpower131 study included patients with squamous histology and other studies were employed in patients with non-squamous NSCLC. The pooled HR for PFS was statistically significant at 0.64 (95% CI: 0.59-0.70; P<0.00001) and the pooled HR for OS was 0.83 (95% CI: 0.75- 0.93; P=0.0008). In non-squamous NSCLC histology group, the pooled HR for PFS was noted at 0.62 (95% CI: 0.56-0.69; P<0.00001) and the pooled HR for OS was 0.79 (95% CI: 0.70- 0.90; P=0.0002). Conclusions Our meta-analysis demonstrated that first-line atezolizumab in combination with chemotherapy significantly improved PFS and OS compared to standard chemotherapy in patients with advanced NSCLC, regardless of the histology. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.