P1.04-78 Efficacy of Checkpoint Inhibitors in Combination with Chemotherapy for First-Line Treatment of Advanced Non-Squamous NSCLC

Checkpoint inhibitors (ipilimumab, nivolumab, pembrolizumab, or atezolizumab) have created a fundamental paradigm shift in the management of non-small cell lung cancer (NSCLC). In recent years, many randomized clinical trials (RCT) have combined different checkpoint inhibitors with various standard chemotherapy regimens as first-line treatment of advanced non-squamous NSCLC. In general, these trials have included patients across different levels of PD-L-1 expression. The purpose of our study is to consolidate the efficacy of checkpoint inhibitors in combination with chemotherapy for first-line treatment of advanced non- squamous NSCLC. We systematically conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs of first-line chemotherapy ± immunotherapy in patients with advanced non-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) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied. A total of 3228 patients with advanced non-squamous NSCLC from 6 RCTs (Keynote – 021,189, IMpower – 130, 132, 150, and Lynch et al.) and a subgroup of another RCT (Checkmate-227) were included. The study arm used standard chemotherapy regimens in combination with ipilimumab, pembrolizumab, atezolizumab, or nivolumab while control arm used only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower-130 and Keynote-189 studies and 1:1 in other studies. The I2statistic for heterogeneity was 15, suggesting some heterogeneity among RCTs. The pooled HR for PFS was statistically significant at 0.61 (95% CI: 0.55-0.67; P <0.00001), and the pooled HR for OS was noted at 0.78 (95% CI: 0.65- 0.94; P = 0.01).The PFS benefit was observed in all PD-L1 categories, including PD-L1 negative/ tumor proportion score (TPS) of less than 1% cohort (HR, 0.67; 95% CI: 0.53- 0.84; P = 0.0005), PD-L1 low/ TPS ≥1-49% cohort (HR, 0.62; 95% CI: 0.52- 0.74; P <0.00001) and PD-L1 high/ TPS ≥50% cohort (HR, 0.42; 95% CI: 0.33- 0.52; P <0.00001). Our study showed that first-line checkpoint inhibitors in combination with chemotherapy significantly improved PFS and OS compared to standard chemotherapy in patients with advanced non-squamous NSCLC and the PFS benefit was consistent regardless of PD-L1 expression.