For frontline NSCLC patients, multiple immune checkpoint inhibitor (ICI) based regimens have shown promising effects on survival outcomes. However, there are currently no studies with direct comparison between the various regimens. The aim of this study was to establish the most effective treatment using a network meta-analysis (NMA) based on all the available randomized controlled trials.
We conducted an independent review for the RCTs evaluating ICIs in frontline advanced NSCLC. A meta-analysis was performed on the primary outcome of OS using the inverse variance heterogeneity method. The Cochrane Q test for heterogeneity was computed and the I2 coefficient was used to quantify the extent of between-study heterogeneity. A threshold for statistical significance of 0.10 was used for the Cochrane Q test and heterogeneity was considered to be substantial if I2> 60%. Since the heterogeneity was found to be both statistically significant and substantial for the primary outcome, it was judged that a pooled analysis would not be representative of the true treatment effect hence a NMA was computed instead. The NMA was computed by utilizing a frequentist approach with generalized pairwise modeling.
Network estimates of effects on OS showed the superiority of pembro+platinum doublet compared to all the other regimens: pembro (HR = 1.39, 95%CI 1.02-1.89); atezo+platinum doublet (HR = 1.72, 95%CI 1.31-2.26); ipi+platinum doublet (HR = 1.62, 95%CI 1.28-2.04), nivo (HR = 1.82, 95%CI 1.35-2.47) and platinum doublet (HR = 1.79, 95%CI 1.49-2.14). The superiority of pembro+platinum doublet was also consistent on PFS except when compared to pembro (HR = 1.78, 95%CI 0.72-4.42) and ORR except when compared to ipi+platinum doublet (HR = 0.33, 95%CI 0.07-1.44), where the comparisons did not reach the threshold of statistical significance.
Our results support the superiority of pembrolizumab + platinum doublet in the frontline treatment of NSCLC. However, the main limitation of this study is that, due to the limited available data, differences in patient and tumor (pathology and PDL-1 status) characteristics could not be accounted for.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.