4.7 Article

The efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as a first-line treatment for advanced lung cancer

Journal

INTERNATIONAL JOURNAL OF CANCER
Volume 142, Issue 11, Pages 2344-2354

Publisher

WILEY
DOI: 10.1002/ijc.31252

Keywords

anti-PD-1/PD-L1 antibodies; anti-CTLA4 antibodies; lung cancer; chemotherapy

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Checkpoint inhibitors show promising efficacy in advanced lung cancer, especially in non-small-cell lung cancer (NSCLC). This meta-analysis was conducted to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as first-line treatments for patients with advanced lung cancer. A systematic search was performed in databases for this system review and quantitative meta-analysis. Twelve trials were finally enrolled in the meta-analysis. Our analyses revealed that the combined overall response rate (ORR) and disease control rate (DCR) for immune checkpoint inhibitors combined with chemotherapy for the treatment of NSCLC were 47.0% (95% CI: 34.2%-60.2%) and 80.9% (95% CI: 69.4%-88.7%), respectively. The combined ORR and DCR for CTLA4 antibody combined with chemotherapy for the treatment of small-cell lung cancer (SCLC) were 65.4% (61.1%-69.5%) and 87.6% (84.5%-90.2%), respectively. The combined six-month progression-free survival rates (PFSRs(6m)) for NSCLC and SCLC were 50.2% (95% CI: 21.9%-78.4%) and 30.7% (21.2%-40.3%), respectively, and the OSRs(1y) were 56.4% (39.1%-73.7%) and 36.9% (33.3%-40.5%), respectively. In addition, the combined ORR and DCR for the checkpoint inhibitors plus CTLA4 antibody treatment group in NSCLC were 29.6% (95% CI: 11.4%-57.8%) and 48.7% (16.8%-81.7%), respectively. In subgroup analyses, a significant improvement in PFS was observed in NSCLC and SCLC, with a combined hazard ratio and 95% confidence interval of 0.841 (0.737-0.961) and 0.856 (0.756-0.968), respectively. In summary, synergistic activity and an acceptable safety profile were observed with checkpoint inhibitor plus chemotherapy combination treatment in lung cancer. What's new? Immune checkpoint inhibitors are effective second-line agents for the treatment of advanced non-small-cell lung cancer (NSCLC). Nonetheless, optimal treatment strategies employing these inhibitors alongside other therapies in NSCLC are yet to be established. The present meta-analysis examined the efficacy of combination therapies using checkpoint inhibitors targeted against programmed death protein 1 (PD-1) or its ligand, PD-L1, with chemotherapy or CTLA4 antibody therapy. Analyses suggest that PD-1/PD-L1 inhibitors and chemotherapy act synergistically to improve progression-free survival but not overall survival. Modest activity and tolerable adverse effects were observed for combined PD-1/PD-L1 inhibitor and CTLA4 antibody therapy.

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