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Factors Modifying the Associations of Single or Combination Programmed Cell Death 1 and Programmed Cell Death Ligand 1 Inhibitor Therapies With Survival Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis
IMPORTANCE: Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors are immune checkpoint inhibitors widely used in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) and other cancers. There is a lack of understanding regarding which factors are associated wi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Medical Association
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838936/ https://www.ncbi.nlm.nih.gov/pubmed/33496794 http://dx.doi.org/10.1001/jamanetworkopen.2020.34201 |
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author | Sati, Neha Boyne, Devon J. Cheung, Winson Y. Cash, Sarah B. Arora, Paul |
author_facet | Sati, Neha Boyne, Devon J. Cheung, Winson Y. Cash, Sarah B. Arora, Paul |
author_sort | Sati, Neha |
collection | PubMed |
description | IMPORTANCE: Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors are immune checkpoint inhibitors widely used in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) and other cancers. There is a lack of understanding regarding which factors are associated with therapeutic response. OBJECTIVES: To conduct a systematic literature review of trials reporting on factors associated with differential response to PD-1/PD-L1 inhibitors among patients diagnosed with metastatic ccRCC and quantitatively synthesize the magnitude to which each factor modified the response to PD-1/PD-L1 inhibitors. DATA SOURCES: The MEDLINE and Cochrane Register of Trials databases were searched for studies published in English from 2006 onward. Searches were last run on September 3, 2019. STUDY SELECTION: This systematic review and meta-analysis assessed 662 phase 2/3 randomized clinical trials that provided subgroup analyses of any baseline characteristics regarding the treatment response to PD-1/PD-L1 inhibitors, alone or as part of a combination therapy, with respect to overall survival (OS) or progression-free survival (PFS) among patients with metastatic ccRCC. DATA EXTRACTION AND SYNTHESIS: A novel quantitative approach was used to synthesize subgroup findings across trials. The ratio of the subgroup-specific hazard ratios (HRs) from each study were pooled using a random-effects meta-analysis whereby ratios of 1.00 would indicate that the subgroup-specific HRs were equal in magnitude. MAIN OUTCOMES AND MEASURES: Main outcomes were OS and PFS. RESULTS: From an initial 662 reports, 7 trials were considered eligible for inclusion. Meta-analyses suggested the treatment response to PD-1/PD-L1 inhibitors in patients with metastatic ccRCC was significantly associated with age (OS: ratio of HR for age ≥75 years to HR for age <65 years, 1.51; 95% CI, 1.01-2.26), PD-L1 expression (PFS: ratio of HR for PD-L1 < 1% to HR for PD-L1 ≥ 10%, 2.21; 95% CI, 1.14-4.27; ratio of HR for PD-L1 < 1% to HR for PD-L1 ≥ 1%, 1.36; 95% CI, 1.10-1.68), Memorial Sloan Kettering Cancer Center risk score (PFS: ratio of HR for immediate risk score to HR for poor risk score, 1.62; 95% CI, 1.14-2.29; ratio of HR for favorable risk score to HR for poor risk score, 1.53; 95% CI, 1.00-2.34; ratio of HR for favorable risk score to HR for intermediate risk score, 0.96; 95% CI, 0.70-1.30), and sarcomatoid tumor presence (PFS: ratio of HR for no sarcomatoid differentiation to HR for sarcomatoid differentiation, 1.54; 95% CI, 1.07-2.21). CONCLUSIONS AND RELEVANCE: This analysis suggests that older age, low levels of PD-L1 expression, and the absence of sarcomatoid tumor differentiation are associated with a diminished response to anti–PD-1/PD-L1 immunotherapies with respect to survival outcomes among patients with metastatic ccRCC. |
format | Online Article Text |
id | pubmed-7838936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-78389362021-02-04 Factors Modifying the Associations of Single or Combination Programmed Cell Death 1 and Programmed Cell Death Ligand 1 Inhibitor Therapies With Survival Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis Sati, Neha Boyne, Devon J. Cheung, Winson Y. Cash, Sarah B. Arora, Paul JAMA Netw Open Original Investigation IMPORTANCE: Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors are immune checkpoint inhibitors widely used in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) and other cancers. There is a lack of understanding regarding which factors are associated with therapeutic response. OBJECTIVES: To conduct a systematic literature review of trials reporting on factors associated with differential response to PD-1/PD-L1 inhibitors among patients diagnosed with metastatic ccRCC and quantitatively synthesize the magnitude to which each factor modified the response to PD-1/PD-L1 inhibitors. DATA SOURCES: The MEDLINE and Cochrane Register of Trials databases were searched for studies published in English from 2006 onward. Searches were last run on September 3, 2019. STUDY SELECTION: This systematic review and meta-analysis assessed 662 phase 2/3 randomized clinical trials that provided subgroup analyses of any baseline characteristics regarding the treatment response to PD-1/PD-L1 inhibitors, alone or as part of a combination therapy, with respect to overall survival (OS) or progression-free survival (PFS) among patients with metastatic ccRCC. DATA EXTRACTION AND SYNTHESIS: A novel quantitative approach was used to synthesize subgroup findings across trials. The ratio of the subgroup-specific hazard ratios (HRs) from each study were pooled using a random-effects meta-analysis whereby ratios of 1.00 would indicate that the subgroup-specific HRs were equal in magnitude. MAIN OUTCOMES AND MEASURES: Main outcomes were OS and PFS. RESULTS: From an initial 662 reports, 7 trials were considered eligible for inclusion. Meta-analyses suggested the treatment response to PD-1/PD-L1 inhibitors in patients with metastatic ccRCC was significantly associated with age (OS: ratio of HR for age ≥75 years to HR for age <65 years, 1.51; 95% CI, 1.01-2.26), PD-L1 expression (PFS: ratio of HR for PD-L1 < 1% to HR for PD-L1 ≥ 10%, 2.21; 95% CI, 1.14-4.27; ratio of HR for PD-L1 < 1% to HR for PD-L1 ≥ 1%, 1.36; 95% CI, 1.10-1.68), Memorial Sloan Kettering Cancer Center risk score (PFS: ratio of HR for immediate risk score to HR for poor risk score, 1.62; 95% CI, 1.14-2.29; ratio of HR for favorable risk score to HR for poor risk score, 1.53; 95% CI, 1.00-2.34; ratio of HR for favorable risk score to HR for intermediate risk score, 0.96; 95% CI, 0.70-1.30), and sarcomatoid tumor presence (PFS: ratio of HR for no sarcomatoid differentiation to HR for sarcomatoid differentiation, 1.54; 95% CI, 1.07-2.21). CONCLUSIONS AND RELEVANCE: This analysis suggests that older age, low levels of PD-L1 expression, and the absence of sarcomatoid tumor differentiation are associated with a diminished response to anti–PD-1/PD-L1 immunotherapies with respect to survival outcomes among patients with metastatic ccRCC. American Medical Association 2021-01-26 /pmc/articles/PMC7838936/ /pubmed/33496794 http://dx.doi.org/10.1001/jamanetworkopen.2020.34201 Text en Copyright 2021 Sati N et al. JAMA Network Open. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the CC-BY-NC-ND License. |
spellingShingle | Original Investigation Sati, Neha Boyne, Devon J. Cheung, Winson Y. Cash, Sarah B. Arora, Paul Factors Modifying the Associations of Single or Combination Programmed Cell Death 1 and Programmed Cell Death Ligand 1 Inhibitor Therapies With Survival Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis |
title | Factors Modifying the Associations of Single or Combination Programmed Cell Death 1 and Programmed Cell Death Ligand 1 Inhibitor Therapies With Survival Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis |
title_full | Factors Modifying the Associations of Single or Combination Programmed Cell Death 1 and Programmed Cell Death Ligand 1 Inhibitor Therapies With Survival Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis |
title_fullStr | Factors Modifying the Associations of Single or Combination Programmed Cell Death 1 and Programmed Cell Death Ligand 1 Inhibitor Therapies With Survival Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis |
title_full_unstemmed | Factors Modifying the Associations of Single or Combination Programmed Cell Death 1 and Programmed Cell Death Ligand 1 Inhibitor Therapies With Survival Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis |
title_short | Factors Modifying the Associations of Single or Combination Programmed Cell Death 1 and Programmed Cell Death Ligand 1 Inhibitor Therapies With Survival Outcomes in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-analysis |
title_sort | factors modifying the associations of single or combination programmed cell death 1 and programmed cell death ligand 1 inhibitor therapies with survival outcomes in patients with metastatic clear cell renal cell carcinoma: a systematic review and meta-analysis |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838936/ https://www.ncbi.nlm.nih.gov/pubmed/33496794 http://dx.doi.org/10.1001/jamanetworkopen.2020.34201 |
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