Differences in oncological and toxicity outcomes between programmed cell death-1 and programmed cell death ligand-1 inhibitors in metastatic renal cell carcinoma: A systematic review and meta-analysis
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Differences in oncological and toxicity outcomes between programmed cell death-1 and programmed cell death ligand-1 inhibitors in metastatic renal cell carcinoma: A systematic review and meta-analysis. / Mori, Keiichiro; Pradere, Benjamin; Quhal, Fahad; Katayama, Satoshi; Mostafaei, Hadi; Laukhtina, Ekaterina; Schuettfort, Victor M; D'Andrea, David; Egawa, Shin; Bensalah, Karim; Schmidinger, Manuela; Powles, Thomas; Shariat, Shahrokh F.
in: CANCER TREAT REV, Jahrgang 99, 102242, 09.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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T1 - Differences in oncological and toxicity outcomes between programmed cell death-1 and programmed cell death ligand-1 inhibitors in metastatic renal cell carcinoma: A systematic review and meta-analysis
AU - Mori, Keiichiro
AU - Pradere, Benjamin
AU - Quhal, Fahad
AU - Katayama, Satoshi
AU - Mostafaei, Hadi
AU - Laukhtina, Ekaterina
AU - Schuettfort, Victor M
AU - D'Andrea, David
AU - Egawa, Shin
AU - Bensalah, Karim
AU - Schmidinger, Manuela
AU - Powles, Thomas
AU - Shariat, Shahrokh F
N1 - Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
PY - 2021/9
Y1 - 2021/9
N2 - BACKGROUND: The programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) pathway is important in metastatic renal cell carcinoma (mRCC). However, some dissimilarities between anti-PD-1 and anti-PD-L1 inhibitors have emerged. We aimed to assess differences between anti-PD-1 and anti-PD-L1 combination immunotherapies as first-line treatments in mRCC patients.METHODS: Multiple databases (PubMed, Web of Science, and Scopus) were searched for articles published until March 2021. Studies were eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORR), complete response rates (CRR), and adverse events.RESULTS: Five studies met the eligibility criteria. PD-1 combination therapy was associated with significantly better OS and PFS and higher ORR and CRR than sunitinib (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.40-0.89; HR: 0.52, 95% CI: 0.37-0.75; odds ratio [OR]: 3.20, 95% CI: 2.18-4.68; and OR: 3.05, 95% CI: 2.13-4.37, respectively; P < 0.001). For all oncological outcomes, anti-PD-1 agents were superior to anti-PD-L1 agents based on HR and OR (OS: HR = 0.88, PFS: HR = 0.76, ORR: OR = 1.85, and CRR: OR = 2.24). Conversely, anti-PD-L1 agents were superior to anti-PD-1 agents in their safety profiles. In network meta-analyses, pembrolizumab plus lenvatinib seemed the worst tolerated anti-PD-1 combination therapy.CONCLUSIONS: Our analysis indicates the superior oncologic benefits of first-line anti-PD-1 combination therapies over anti-PD-L1 combination therapies in mRCC patients. This biological difference is of vital importance for clinical treatment decision making and the design of future rational combination therapy trials in mRCC.
AB - BACKGROUND: The programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) pathway is important in metastatic renal cell carcinoma (mRCC). However, some dissimilarities between anti-PD-1 and anti-PD-L1 inhibitors have emerged. We aimed to assess differences between anti-PD-1 and anti-PD-L1 combination immunotherapies as first-line treatments in mRCC patients.METHODS: Multiple databases (PubMed, Web of Science, and Scopus) were searched for articles published until March 2021. Studies were eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORR), complete response rates (CRR), and adverse events.RESULTS: Five studies met the eligibility criteria. PD-1 combination therapy was associated with significantly better OS and PFS and higher ORR and CRR than sunitinib (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.40-0.89; HR: 0.52, 95% CI: 0.37-0.75; odds ratio [OR]: 3.20, 95% CI: 2.18-4.68; and OR: 3.05, 95% CI: 2.13-4.37, respectively; P < 0.001). For all oncological outcomes, anti-PD-1 agents were superior to anti-PD-L1 agents based on HR and OR (OS: HR = 0.88, PFS: HR = 0.76, ORR: OR = 1.85, and CRR: OR = 2.24). Conversely, anti-PD-L1 agents were superior to anti-PD-1 agents in their safety profiles. In network meta-analyses, pembrolizumab plus lenvatinib seemed the worst tolerated anti-PD-1 combination therapy.CONCLUSIONS: Our analysis indicates the superior oncologic benefits of first-line anti-PD-1 combination therapies over anti-PD-L1 combination therapies in mRCC patients. This biological difference is of vital importance for clinical treatment decision making and the design of future rational combination therapy trials in mRCC.
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - B7-H1 Antigen/antagonists & inhibitors
KW - Carcinoma, Renal Cell/drug therapy
KW - Clinical Trials, Phase III as Topic
KW - Humans
KW - Immune Checkpoint Inhibitors/administration & dosage
KW - Kidney Neoplasms/drug therapy
KW - Programmed Cell Death 1 Receptor/antagonists & inhibitors
KW - Randomized Controlled Trials as Topic
U2 - 10.1016/j.ctrv.2021.102242
DO - 10.1016/j.ctrv.2021.102242
M3 - SCORING: Review article
C2 - 34153830
VL - 99
JO - CANCER TREAT REV
JF - CANCER TREAT REV
SN - 0305-7372
M1 - 102242
ER -
