P2.04-86 Efficacy of Ipilimumab in Combination with Chemotherapy for First-Line Treatment of Advanced Lung Cancer

Abstract

Lung cancer is the second most common cancer in both sexes and is the leading cause of cancer mortality in the United States. Combination of checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab, or atezolizumab) and chemotherapy has shown synergistic anti-tumor activities and has created a fundamental paradigm shift in the management of first-line treatment of advanced lung cancer. We performed a systematic review and meta-analysis of currently available randomized controlled trials (RCTs) to evaluate the efficacy of ipilimumab in combination with chemotherapy for the first-line treatment of advanced lung cancer. We systematically conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs utilizing first-line ipilimumab chemoimmunotherapy in patients with advanced lung cancer 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) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q -statistic. Random effects model was applied. A total of 3178 patients with advanced lung cancer from 5 RCTs were included in the analysis. The study arm used standard chemotherapy regimens in combination with ipilimumab while control arm used only standard chemotherapy regimens. The randomization ratio was 1:1 in all studies. Ipilimumab was employed either in phased or concurrent with chemotherapy. The I2statistic for heterogeneity was 63%, suggesting some heterogeneity among RCTs. The pooled HR for PFS was significant at 0.85 (95% CI: 0.78-0.93; P = 0.0004) when ipilimumab was utilized in phased with chemotherapy. In non-small cell lung cancer population, the pooled HR for PFS was noted at 0.82 (95% CI: 0.68-1.00; P = 0.05), and the pooled HR for OS was 0.92 (95% CI: 0.83- 1.02; P = 0.10). In patients with extensive-stage small cell lung cancer, the pooled HR for PFS was statistically significant at 0.86 (95% CI: 0.77-0.97; P = 0.01), and the pooled HR for OS was 0.92 (95% CI: 0.81-1.06; P = 0.26). Our meta-analysis depicted that upfront ipilimumab chemoimmunotherapy significantly improved PFS compared to standard chemotherapy, when ipilimumab was either employed in phased with chemotherapy or in patients with extensive-stage small cell lung cancer.