Rational application of the first‐line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta‐analysis

• Published in: Cancer medicine (Malden, MA) Vol. 8; no. 11; pp. 5033 - 5046
• Main Authors: Cao, Rui, Ma, Jie‐Tao, Zhang, Shu‐Ling, Sun, Li, Liu, Yang, Zhang, Xiang‐Yan, Jing, Wei, Huang, Le‐Tian, Han, Cheng‐Bo
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2019; John Wiley and Sons Inc; Wiley
• Subjects: Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Biomarkers; Biomarkers, Tumor; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - etiology; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Clinical Cancer Research; Clinical trials; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Immune checkpoint inhibitors; Immunotherapy; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - etiology; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Meta-analysis; Molecular Targeted Therapy - adverse effects; Molecular Targeted Therapy - methods; Monoclonal antibodies; Non-small cell lung carcinoma; nonsmall cell lung cancer; Original Research; PD-L1 protein; Pembrolizumab; programmed death‐ligand 1; Publication Bias; Remission Induction; Software; Studies; Targeted cancer therapy; Treatment Outcome; meta-analysis; programmed death-ligand 1; chemotherapy; nonsmall cell lung cancer; immunotherapy
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2407

Objective To compare the relative efficacy of immune checkpoint inhibitors (ICIs) or chemotherapy (CT) alone, or their combination modality in the first‐line treatment of advanced nonsmall cell lung cancer (NSCLC). Methods This meta‐analysis was performed on the eligible randomized controlled trials (RCTs) after searching web databases and meeting s. The main research endpoints were the comparisons of median overall survival (mOS), the OS rate of 6 months (OSR6m), 1 year (OSR1y) and 2 years (OSR2y), median progression‐free survival (mPFS), the PFS rate of 6 months (PFSR6m) and 1‐year (PFSR1y), objective response rates (ORR), and treatment‐related adverse events (TRAEs). Results Eleven RCTs comprising 6278 cases were included. In the subgroup of programmed death‐ligand 1 (PD‐L1) ≥50%, compared with chemotherapy, the ICIs showed similar OSR6m (P > 0.05), but significantly improved efficacy in mOS, OSR1y, OSR2y, and ORR (all P < 0.05), also had less grade ≥ 3 TRAEs. Compared with pembrolizumab alone, pembrolizumab plus CT in the subgroup of PD‐L1 ≥ 50% had similar mOS, OSR6m, OSR1y, and PFSR1y (all P > 0.05), but significantly improved mPFS, PFSR6m, and ORR (all P < 0.05 for interaction). Compared with the CT group, ICIs plus CT group with PD‐L1 ≥ 50% or <1% showed significant benefit in OS, PFS, and ORR (all P < 0.05). However, in the ICIs plus CT group with 1% ≤ PD‐L1 ≤ 49%, only PFS and ORR showed significant benefit compared with CT group (all P < 0.05), but not for results of OS. Conclusions The findings support the rationale for using pembrolizumab alone in the first‐line treatment of PD‐L1 ≥ 50% advanced NSCLC due to the similar OS and lower grade ≥ 3 TRAEs. However, the combination of ICIs and chemotherapy is strongly recommended in patients with PD‐L1 ≤ 49% for significant survival benefit. Immune checkpoint inhibitors (ICIs) in combination with chemotherapy significantly improve the disease control and reduce the risk of disease progression but have no statistically significant survival benefits compared with ICIs alone in the first‐line treatment of PD‐L1 high expression (TPS ≥ 50%) advanced NSCLC. The findings support the rationale for using pembrolizumab alone in the treatment of advanced NSCLC with PD‐L1 ≥ 50%. However, a significant survival benefit compared with chemotherapy alone even in PD‐L1 low or negative expression advanced NSCLC was observed in combination therapy, but it was associated with a higher incidence of grade ≥ 3 TRAEs.