Efficacy of immune checkpoint inhibitors (ICIs) in advanced large cell neuroendocrine carcinoma (LCNEC) of the lung: A systematic review and meta-analysis.

Abstract

8576 Background: LCNEC of the lung is a high-grade neuroendocrine carcinoma with characteristics of both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Guidelines for optimal treatment for LCNEC are lacking due to the paucity of randomized control trials. Treatment regimens are often extrapolated from SCLC and NSCLC. Immunotherapy has revolutionized the outcomes of solid malignancies, including lung cancers, in the past decade. In this study, we assess the efficacy of ICIs in advanced LCNEC. Methods: A systematic literature search was conducted on PubMed, Embase, and Google Scholar for studies assessing the role of ICIs in advanced LCNEC of the lung. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. A random effects model was used to pool the outcomes along with 95% confidence intervals (CI). Statistical analyses were performed using program R version 4.4.1. Results: We included 12 studies- 11 retrospective and 1 prospective analysis. The total number of advanced LCNEC patients across all the studies was 470. 241 patients received ICIs in total, either as monotherapy or in combination with chemotherapy or anti-angiogenic agents. The pooled Objective Response Rate (ORR) for patients receiving ICIs was 34.71% (95% CI: 27.75-41.97, I 2 : 26.2%), whereas the pooled Disease Control Rate (DCR) was 71.87% (95% CI: 59.57-82.92, I 2 : 67.7%). The most common ICIs across the cohort were atezolizumab, camrelizumab, nivolumab, and pembrolizumab. A subgroup analysis of three double-arm studies comparing chemotherapy alone (n=42) versus a combination of chemotherapy and ICIs (n=42) as a first-line treatment was performed. We found a favoring trend of the combination over chemotherapy alone for ORR (RR=1.58, 95% CI: 0.92-2.70; p=0.095), although non-significant, but significant advantage for DCR (RR=1.32, 95% CI: 1.04-1.68; p=0.021). Conclusions: ICIs have become the standard of care for treating SCLC and NSCLC in various combinations. ICIs, based on our meta-analysis, have also demonstrated encouraging results in advanced LCNEC. However, tumor factors such as molecular subtypes, genomic profiles, and other predictors influencing the response to ICIs need to be elucidated. Further larger prospective studies are awaited to determine their potential in this rare but aggressive subtype of lung cancer.