Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Marina D. Kaymakcalan, Wanling Xie, Laurence Albiges, Scott A. North, Christian K. Kollmannsberger, Martin Smoragiewicz, Nils Kroeger, J. Connor Wells, SunYoung Rha, Jae Lyun Lee, Rana R. McKay, André P. Fay, Guillermo De Velasco, Daniel Y.C. Heng, Toni K. Choueiri

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Abstract

BACKGROUND Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. METHODS The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. RESULTS Overall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age ≥60 years, a glomerular filtration rate (GFR) <30 mL/min/1.73 m 2 , a single metastatic site, and a sodium level <135 mmol/L. A risk group model was developed that used the number of patient risk factors to predict the risk of TrTD. CONCLUSIONS In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice. Cancer 2016;122:411-419.

Original languageEnglish
Pages (from-to)411-419
Number of pages9
JournalCancer
Volume122
Issue number3
DOIs
Publication statusPublished - 2016 Feb 1

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Renal Cell Carcinoma
Vascular Endothelial Growth Factor A
Databases
Therapeutics
Glomerular Filtration Rate
Sodium
Mucositis
Fatigue
Diarrhea

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kaymakcalan, Marina D. ; Xie, Wanling ; Albiges, Laurence ; North, Scott A. ; Kollmannsberger, Christian K. ; Smoragiewicz, Martin ; Kroeger, Nils ; Wells, J. Connor ; Rha, SunYoung ; Lee, Jae Lyun ; McKay, Rana R. ; Fay, André P. ; De Velasco, Guillermo ; Heng, Daniel Y.C. ; Choueiri, Toni K. / Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy : Results from the International Metastatic Renal Cell Carcinoma Database Consortium. In: Cancer. 2016 ; Vol. 122, No. 3. pp. 411-419.
@article{702c66e8179641c68d499fbebd20e692,
title = "Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium",
abstract = "BACKGROUND Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. METHODS The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. RESULTS Overall, 198 (23.8{\%}) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77{\%}), and it was followed by sorafenib (18.4{\%}). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age ≥60 years, a glomerular filtration rate (GFR) <30 mL/min/1.73 m 2 , a single metastatic site, and a sodium level <135 mmol/L. A risk group model was developed that used the number of patient risk factors to predict the risk of TrTD. CONCLUSIONS In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice. Cancer 2016;122:411-419.",
author = "Kaymakcalan, {Marina D.} and Wanling Xie and Laurence Albiges and North, {Scott A.} and Kollmannsberger, {Christian K.} and Martin Smoragiewicz and Nils Kroeger and Wells, {J. Connor} and SunYoung Rha and Lee, {Jae Lyun} and McKay, {Rana R.} and Fay, {Andr{\'e} P.} and {De Velasco}, Guillermo and Heng, {Daniel Y.C.} and Choueiri, {Toni K.}",
year = "2016",
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Kaymakcalan, MD, Xie, W, Albiges, L, North, SA, Kollmannsberger, CK, Smoragiewicz, M, Kroeger, N, Wells, JC, Rha, S, Lee, JL, McKay, RR, Fay, AP, De Velasco, G, Heng, DYC & Choueiri, TK 2016, 'Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium', Cancer, vol. 122, no. 3, pp. 411-419. https://doi.org/10.1002/cncr.29773

Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy : Results from the International Metastatic Renal Cell Carcinoma Database Consortium. / Kaymakcalan, Marina D.; Xie, Wanling; Albiges, Laurence; North, Scott A.; Kollmannsberger, Christian K.; Smoragiewicz, Martin; Kroeger, Nils; Wells, J. Connor; Rha, SunYoung; Lee, Jae Lyun; McKay, Rana R.; Fay, André P.; De Velasco, Guillermo; Heng, Daniel Y.C.; Choueiri, Toni K.

In: Cancer, Vol. 122, No. 3, 01.02.2016, p. 411-419.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy

T2 - Results from the International Metastatic Renal Cell Carcinoma Database Consortium

AU - Kaymakcalan, Marina D.

AU - Xie, Wanling

AU - Albiges, Laurence

AU - North, Scott A.

AU - Kollmannsberger, Christian K.

AU - Smoragiewicz, Martin

AU - Kroeger, Nils

AU - Wells, J. Connor

AU - Rha, SunYoung

AU - Lee, Jae Lyun

AU - McKay, Rana R.

AU - Fay, André P.

AU - De Velasco, Guillermo

AU - Heng, Daniel Y.C.

AU - Choueiri, Toni K.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - BACKGROUND Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. METHODS The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. RESULTS Overall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age ≥60 years, a glomerular filtration rate (GFR) <30 mL/min/1.73 m 2 , a single metastatic site, and a sodium level <135 mmol/L. A risk group model was developed that used the number of patient risk factors to predict the risk of TrTD. CONCLUSIONS In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice. Cancer 2016;122:411-419.

AB - BACKGROUND Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. METHODS The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. RESULTS Overall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age ≥60 years, a glomerular filtration rate (GFR) <30 mL/min/1.73 m 2 , a single metastatic site, and a sodium level <135 mmol/L. A risk group model was developed that used the number of patient risk factors to predict the risk of TrTD. CONCLUSIONS In the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice. Cancer 2016;122:411-419.

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U2 - 10.1002/cncr.29773

DO - 10.1002/cncr.29773

M3 - Article

C2 - 26540173

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