A pooled meta-analysis of PD-1/L1 inhibitors incorporation therapy for advanced non-small cell lung cancer
Authors Wan N, Ji B, Li J, Jiang J, Yang C, Zhang T, Huang W
Received 6 January 2019
Accepted for publication 4 April 2019
Published 27 June 2019 Volume 2019:12 Pages 4955—4973
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Sanjay Singh
Ning Wan,1,2,* Bo Ji,1,* Jian Li,1 Jie Jiang,3 Chen Yang,1 Tiantian Zhang,3 Wenjie Huang4
1Department of Pharmacy, General Hospital of Southern Theater Command, Guangzhou, Guangdong Province 510010, People’s Republic of China; 2Post-doctoral Research Station, Guangzhou Huabo Biopharmaceutical Research Institute, Guangzhou, Guangdong Province 510010, People’s Republic of China; 3College of Pharmacy, Jinan University, Guangzhou, Guangdong Province 510632, People’s Republic of China; 4Department of Respiratory Medicine, General Hospital of Southern Theater Command, Guangzhou, Guangdong Province 510010, People’s Republic of China
*These authors contributed equally to this work
Objective: Immune checkpoint inhibitors, especially the programmed cell death receptor-1/ligand 1 (PD-1/L1) inhibitors, displayed promising efficacy in non-small cell lung cancer (NSCLC) patients. Incorporation of anti-PD-1/L1 antibodies into other therapeutic regimens (including CTLA-4 inhibitors, chemotherapy, EGFR-TKIs and IDO inhibitors) is currently in active clinical research. This meta-analysis summarized recent developments in four combination regimens of PD-1/L1 inhibitors.
Methods: We searched PubMed, the Cochrane Library and the Embase database up to July 2018, on the combination therapy of PD-1/L1 inhibitors in NSCLC patients.
Results: Seventeen trials were finally included in the current meta-analysis. The combined objective response rates (ORR) for PD-1/L1 inhibitors in combination with CTLA-4 inhibitors, chemotherapy, EGFR-TKIs, and IDO inhibitors were 32% (19%–44%), 49% (46%–53%), 55% (28%–83%) and 35% (20%–50%) respectively. The combined ORR for first line PD-1/L1 inhibitors combination with CTLA-4 inhibitors, chemotherapy, and EGFR-TKIs were 35% (17%–53%), 51% (46%–56%) and 43% (−7%–93%) respectively, and the combined ORR in the second or more line setting were 36% (8%–65%), 17% (−13%–46%), 39% (19%–59%) and 35% (20%–50%) respectively. The pooled 6-month progression-free survival rate (6m PFSr) and 1-year overall survival rate (1y OSr) for combination therapy of PD-1/L1 inhibitors with CTLA-4 inhibitors or chemotherapy were 35% or 65% (6m PFSr) and 31% or 70% (1y OSr) respectively. Anti-PD-1/L1 drugs combined with anti-CTLA-4 drugs exhibited a more potent efficacy on PD-L1 positive patients (OR=0.33, 95%CI: 0.12–0.88). This trend was not observed in patients receiving combination therapy of PD-1/L1 inhibitors with chemotherapy (OR=0.96, 95%CI: 0.51–1.78).
Conclusion: The included four combination regimens were potential treatment strategies and well tolerated for NSCLC patients. Further, the therapy lines and PD-L1 expression status were correlated with treatment efficacy.
Keywords: PD-1/L1 inhibitors, combination therapy, meta-analysis, non-small cell lung cancer
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]