Article Abstract

Impact of clinicopathological features on the efficacy of immune checkpoint inhibitors plus conventional treatment in patients with advanced lung cancer

Authors: Guanghui Gao, Meng Qiao, Hongcheng Liu, Tao Jiang, Fei Zhou, Xuefei Li, Chao Zhao, Xiaoxia Chen, Chunxia Su, Shengxiang Ren, Caicun Zhou


Background: To investigate the impact of different immune checkpoint inhibitors (ICI), programmed-death ligand 1 (PD-L1) expression and clinical characteristics on clinical outcome of ICI plus conventional treatment in advanced lung cancer patients.
Methods: Randomized clinical trials that compared combination therapy versus control group were screened in PubMed, EMBASE, Web of Science, Cochrane Library and included. The pooled hazard ratio (HR) with a 95% confidence interval (95% CI) were used to estimate associations. Cochrane Collaboration tool was used for quality assessment.
Results: Thirteen clinical trials were included (n=9,241). The pooled results indicated that combination strategy based on ICI significantly improved PFS (HR =0.66, P<0.001) and OS (HR =0.77, P<0.001) in overall population. Greatest PFS improvement was seen in group of PD-1 based combination (HR =0.54, P<0.001), followed by PD-L1 based (HR =0.66, P<0.001) and CTLA-4 based combination (HR =0.86, P=0.002) (interaction: P<0.001).The improvement in PFS did proportionally differ by PD-L1 expression (interaction: P<0.001). OS HRs favored combination in patients with negative or strong positive group of PD-L1 expression not in the group of weak positive group (HR =0.77, P=0.12). Subgroup analysis demonstrated that OS benefit could be observed in male (HR =0.82, P=0.03), current or former smokers (HR =0.74, P=0.04), non-squamous (HR =0.71, P<0.001) and patients without driver mutations (HR =0.73, P<0.001). OS benefit rather than PFS benefit was appeared in patients with liver metastasis treated with ICI-based combination (HR =0.74, P=0.005).
Conclusions: ICI plus conventional treatment could significantly improve PFS and OS in overall advanced lung cancer patients. PD-1-based combination leads to the greatest improvement in both PFS and OS. More data are warranted to address the association of PD-L1 staining intensity with OS improvement. Male, current or former smokers, non-squamous and patients without driver mutations do benefit from ICI-based combination.