Guanghui Gao1,2, Meng Qiao2, Hongcheng Liu3, Tao Jiang2, Fei Zhou2, Xuefei Li4, Chao Zhao4, Xiaoxia Chen2, Chunxia Su2, Shengxiang Ren2, Caicun Zhou2. 1. Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213000, China. 2. Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. 3. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. 4. Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
Abstract
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. 2019 Journal of Thoracic Disease. All rights reserved.
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. 2019 Journal of Thoracic Disease. All rights reserved.
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