TY - JOUR
T1 - Use of Immunotherapy with Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients with Cancer
T2 - A Systematic Review and Meta-analysis
AU - Duan, Jianchun
AU - Cui, Longgang
AU - Zhao, Xiaochen
AU - Bai, Hua
AU - Cai, Shangli
AU - Wang, Guoqiang
AU - Zhao, Zhengyi
AU - Zhao, Jing
AU - Chen, Shiqing
AU - Song, Jia
AU - Qi, Chuang
AU - Wang, Qing
AU - Huang, Mengli
AU - Zhang, Yuzi
AU - Huang, Depei
AU - Bai, Yuezong
AU - Sun, Feng
AU - Lee, J. Jack
AU - Wang, Jie
AU - Wang, Zhijie
N1 - Funding Information:
M. Huang, Zhang, D. Huang, and Bai are employees of 3D Medicines Inc. No other conflicts were reported. Funding/Support:Supportforthestudywasprovided by China National Natural Sciences Foundation Key Program grants 81630071 and 81330062 (J. Wang), National Key R&D Program of China grant 2016YFC0902300 (J. Wang), and China National NaturalSciencesFoundationgrant81871889)(Z.Wang). RoleoftheFunder/Sponsor:Thefundingorganizations had no role in the design and conduct of the study; collection,management,analysis,andinterpretationof the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Additional Contributions: Lei Yang, MD, and Zhili Fang, PhD (The Medical Department, 3D Medicines Inc, Shanghai, China), contributed to the initial literature review. There was no financial compensation outside of salary.
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2020/3
Y1 - 2020/3
N2 - Importance: Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice. Objective: To assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types. Data Sources: Systematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to March 1, 2019. In addition, abstracts and presentations from all major conference proceedings were reviewed. Study Selection: All randomized clinical trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with cancer were selected as candidates. Retrospective studies, single-arm phase 1/2 studies, and trials comparing anti-PD-1 and anti-PD-L1 with other immunotherapies were excluded. Studies of anti-PD-1 and anti-PD-L1 therapy were screened and paired by the matching of clinical characteristics as mirror groups. Data Extraction and Synthesis: Three investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Trial names, first author, year of publication, study design, National Clinical Trial identifier number, blinding status, study phase, pathologic characteristics, number of patients, patients' age and sex distribution, Eastern Cooperative Oncology Group Performance Status, lines of treatment, study drugs, biomarker status, follow-up time, incidence of adverse events, and hazard ratios (HRs) with 95% CIs for overall survival and progression-free survival were extracted. A random-effects model was applied for data analysis. Main Outcomes and Measures: Differences in OS between anti-PD-1 and anti-PD-L1 across different cancer types were assessed. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Results: Nineteen randomized clinical trials involving 11379 patients were included in the meta-analysis. Overall, anti-PD-1 exhibited superior overall survival (HR, 0.75; 95% CI, 0.65-0.86; P <.001) and progression-free survival (HR, 0.73; 95% CI, 0.56-0.96; P =.02) compared with anti-PD-L1. No significant difference was observed in their safety profiles. Sensitivity analysis presented consistency in the overall estimates across these analyses. Consistent results were observed through frequentist and bayesian approaches with the same studies. Conclusions and Relevance: Comprehensive analysis suggests that anti-PD-1 exhibited favorable survival outcomes and a safety profile comparable to that of anti-PD-L1, which may provide a useful guide for clinicians.
AB - Importance: Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice. Objective: To assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types. Data Sources: Systematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to March 1, 2019. In addition, abstracts and presentations from all major conference proceedings were reviewed. Study Selection: All randomized clinical trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with cancer were selected as candidates. Retrospective studies, single-arm phase 1/2 studies, and trials comparing anti-PD-1 and anti-PD-L1 with other immunotherapies were excluded. Studies of anti-PD-1 and anti-PD-L1 therapy were screened and paired by the matching of clinical characteristics as mirror groups. Data Extraction and Synthesis: Three investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Trial names, first author, year of publication, study design, National Clinical Trial identifier number, blinding status, study phase, pathologic characteristics, number of patients, patients' age and sex distribution, Eastern Cooperative Oncology Group Performance Status, lines of treatment, study drugs, biomarker status, follow-up time, incidence of adverse events, and hazard ratios (HRs) with 95% CIs for overall survival and progression-free survival were extracted. A random-effects model was applied for data analysis. Main Outcomes and Measures: Differences in OS between anti-PD-1 and anti-PD-L1 across different cancer types were assessed. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Results: Nineteen randomized clinical trials involving 11379 patients were included in the meta-analysis. Overall, anti-PD-1 exhibited superior overall survival (HR, 0.75; 95% CI, 0.65-0.86; P <.001) and progression-free survival (HR, 0.73; 95% CI, 0.56-0.96; P =.02) compared with anti-PD-L1. No significant difference was observed in their safety profiles. Sensitivity analysis presented consistency in the overall estimates across these analyses. Consistent results were observed through frequentist and bayesian approaches with the same studies. Conclusions and Relevance: Comprehensive analysis suggests that anti-PD-1 exhibited favorable survival outcomes and a safety profile comparable to that of anti-PD-L1, which may provide a useful guide for clinicians.
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U2 - 10.1001/jamaoncol.2019.5367
DO - 10.1001/jamaoncol.2019.5367
M3 - Article
C2 - 31876895
AN - SCOPUS:85077228580
SN - 2374-2437
VL - 6
SP - 375
EP - 384
JO - JAMA Oncology
JF - JAMA Oncology
IS - 3
ER -