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, Sun Young
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.
N1 - Publisher Copyright:
© 2015 American Cancer Society.
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 m2, 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 m2, 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.
KW - International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)
KW - VEGF-targeted therapies
KW - model
KW - renal cell carcinoma
KW - risk factors
KW - toxicity
KW - treatment discontinuation
UR - http://www.scopus.com/inward/record.url?scp=84948808287&partnerID=8YFLogxK
U2 - 10.1002/cncr.29773
DO - 10.1002/cncr.29773
M3 - Article
C2 - 26540173
AN - SCOPUS:84948808287
SN - 0008-543X
VL - 122
SP - 411
EP - 419
JO - Cancer
JF - Cancer
IS - 3
ER -