Predictors of survival benefit from immune checkpoint inhibitors in patients with advanced non-small cell lung cancer: A systematic review and meta-analysis

Abstract Introduction Randomized trials showed inconsistent survival benefit with immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with low PD-L1 tumors ( 65 years old) and never-smokers. We conducted a systematic review and meta-analysis to assess the efficacy of single agent ICIs in these pre-defined subgroups. Methods The electronic databases PubMed and EMBASE, were searched for relevant randomized trials. Pooled hazard ratios (HR) for overall survival (OS) and progression free survival (PFS) were meta-analyzed using the generic inverse variance method.. Results Nine studies were included. Compared to chemotherapy, the use of single agent ICIs in the second line setting reduced the risk of death independent of PD-L1 expression (HR 0.79, 95%CI 0.66-0.96 and HR 0.75, 95%CI 0.61-0.85 for patients with PD-L1 (-) and (+) tumors, respectively). Yet, a PFS benefit was only seen in patients with PD-L1 (+) tumors. Similarly, an OS benefit was seen in patients independent of age (HR 0.79, 95%CI 0.69-0.89 and HR 0.76, 95%CI 0.66-0.88 for elderly and non-elderly patients, respectively). Conversely, an OS benefit was only seen in ever-smokers (HR 0.78, 95%CI 0.68-0.89) and a detrimental effect on PFS in never-smokers (HR 1.68, 95%CI 1.07-2.63). Conclusions Advanced NSCLC patients derive a survival benefit from ICIs independent of tumor PD-L1 expression and age particularly in the second line while never-smokers do not. Caution should be exercised when offering single agent ICIs to elderly patients in the first line and other treatment options should be considered in never smokers.