First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis [Figure presented]

Christopher J.D. Wallis, Zachary W A Klaassen, Bimal Bhindi, Xiang Y. Ye, Thenappan Chandrasekar, Ann M. Farrell, Hanan Goldberg, Stephen A. Boorjian, Bradley Leibovich, Girish S. Kulkarni, Prakesh S. Shah, Georg A. Bjarnason, Daniel Y.C. Heng, Raj Satkunasivam, Antonio Finelli

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Context: In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. Objective: To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. Evidence acquisition: Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes. Evidence synthesis: In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs. Conclusions: Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials. Patient summary: There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation. There are many options for first-line therapy in metastatic renal cell carcinoma. However, there is a paucity of comparative data. Using a network meta-analysis approach, we found that cabozantanib and nivolumab plus ipilimumab are likely to be preferable agents in this space. However, these findings require validation in direct comparative studies.

Original languageEnglish (US)
Pages (from-to)309-321
Number of pages13
JournalEuropean Urology
Volume74
Issue number3
DOIs
StatePublished - Sep 1 2018
Externally publishedYes

Fingerprint

Renal Cell Carcinoma
Therapeutics
Disease-Free Survival
Databases
Network Meta-Analysis
Survival
Medical Societies
Decision Making
Randomized Controlled Trials
ipilimumab
nivolumab
Safety

Keywords

  • Cabozantinib
  • Disease-free survival
  • Network meta-analysis
  • Nivolumab
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

First-line Systemic Therapy for Metastatic Renal Cell Carcinoma : A Systematic Review and Network Meta-analysis [Figure presented]. / Wallis, Christopher J.D.; Klaassen, Zachary W A; Bhindi, Bimal; Ye, Xiang Y.; Chandrasekar, Thenappan; Farrell, Ann M.; Goldberg, Hanan; Boorjian, Stephen A.; Leibovich, Bradley; Kulkarni, Girish S.; Shah, Prakesh S.; Bjarnason, Georg A.; Heng, Daniel Y.C.; Satkunasivam, Raj; Finelli, Antonio.

In: European Urology, Vol. 74, No. 3, 01.09.2018, p. 309-321.

Research output: Contribution to journalReview article

Wallis, CJD, Klaassen, ZWA, Bhindi, B, Ye, XY, Chandrasekar, T, Farrell, AM, Goldberg, H, Boorjian, SA, Leibovich, B, Kulkarni, GS, Shah, PS, Bjarnason, GA, Heng, DYC, Satkunasivam, R & Finelli, A 2018, 'First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis [Figure presented]', European Urology, vol. 74, no. 3, pp. 309-321. https://doi.org/10.1016/j.eururo.2018.03.036
Wallis, Christopher J.D. ; Klaassen, Zachary W A ; Bhindi, Bimal ; Ye, Xiang Y. ; Chandrasekar, Thenappan ; Farrell, Ann M. ; Goldberg, Hanan ; Boorjian, Stephen A. ; Leibovich, Bradley ; Kulkarni, Girish S. ; Shah, Prakesh S. ; Bjarnason, Georg A. ; Heng, Daniel Y.C. ; Satkunasivam, Raj ; Finelli, Antonio. / First-line Systemic Therapy for Metastatic Renal Cell Carcinoma : A Systematic Review and Network Meta-analysis [Figure presented]. In: European Urology. 2018 ; Vol. 74, No. 3. pp. 309-321.
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abstract = "Context: In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. Objective: To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. Evidence acquisition: Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes. Evidence synthesis: In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91{\%}) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48{\%} chance that nivolumab plus ipilimumab was the preferred option. There was a 67{\%} likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs. Conclusions: Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials. Patient summary: There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation. There are many options for first-line therapy in metastatic renal cell carcinoma. However, there is a paucity of comparative data. Using a network meta-analysis approach, we found that cabozantanib and nivolumab plus ipilimumab are likely to be preferable agents in this space. However, these findings require validation in direct comparative studies.",
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TY - JOUR

T1 - First-line Systemic Therapy for Metastatic Renal Cell Carcinoma

T2 - A Systematic Review and Network Meta-analysis [Figure presented]

AU - Wallis, Christopher J.D.

AU - Klaassen, Zachary W A

AU - Bhindi, Bimal

AU - Ye, Xiang Y.

AU - Chandrasekar, Thenappan

AU - Farrell, Ann M.

AU - Goldberg, Hanan

AU - Boorjian, Stephen A.

AU - Leibovich, Bradley

AU - Kulkarni, Girish S.

AU - Shah, Prakesh S.

AU - Bjarnason, Georg A.

AU - Heng, Daniel Y.C.

AU - Satkunasivam, Raj

AU - Finelli, Antonio

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Context: In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. Objective: To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. Evidence acquisition: Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes. Evidence synthesis: In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs. Conclusions: Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials. Patient summary: There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation. There are many options for first-line therapy in metastatic renal cell carcinoma. However, there is a paucity of comparative data. Using a network meta-analysis approach, we found that cabozantanib and nivolumab plus ipilimumab are likely to be preferable agents in this space. However, these findings require validation in direct comparative studies.

AB - Context: In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. Objective: To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. Evidence acquisition: Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes. Evidence synthesis: In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs. Conclusions: Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials. Patient summary: There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation. There are many options for first-line therapy in metastatic renal cell carcinoma. However, there is a paucity of comparative data. Using a network meta-analysis approach, we found that cabozantanib and nivolumab plus ipilimumab are likely to be preferable agents in this space. However, these findings require validation in direct comparative studies.

KW - Cabozantinib

KW - Disease-free survival

KW - Network meta-analysis

KW - Nivolumab

KW - Renal cell carcinoma

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