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

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.