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.
Bibliographical noteFunding Information:
This study was funded by the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute (to Toni K. Choueiri), the Dana-Farber/Harvard Cancer Center Kidney Cancer Program, and the Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Program of Research Excellence (P50 CA101942-01). The funding sources had no role in the study design, analysis, interpretation, or writing of the article. Marina D. Kaymakcalan, Wanling Xie, Martin Smoragiewicz, J. Connor Wells, and Andr? P. Fay report no disclosures. Guillermo De Velasco reports that his wife worked as a bank physician at GlaxoSmithKline until February 2015. Nils Kroeger reports personal fees from Bristol-Myers Squibb and Pfizer Oncology outside the submitted work and travel support from Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, and Astellas. Laurence Albiges reports serving on advisory boards for Bristol-Myers Squibb, Novartis, Pfizer, Bayer, Sanofi, and Amgen and receiving research funding from Novartis and Pfizer. Scott A. North reports serving on advisory boards and acting as a consultant for Novartis, Bayer, GlaxoSmithKline, and Pfizer and receiving honoraria from Astellas, Sanofi, Janssen, Novartis, and Pfizer outside the submitted work. Christian K. Kollmannsberger reports serving on advisory boards and receiving honoraria/funding from Pfizer, Novartis, Sanofi, Bristol-Myers Squibb, and GlaxoSmithKline. Sun-Young Rha reports serving on advisory boards for Novartis, Pfizer, and GlaxoSmithKline and receiving funding from Novartis and Bayer Korea. J. Connor Wells reports serving on an advisory board and acting as a consultant for Astellas Pharma and receiving honoraria/funding from Pfizer. Rana R. McKay reports receiving research funding from Pfizer and Bayer. Daniel Y. C. Heng reports serving on advisory boards and acting as a consultant for Pfizer, Novartis, and Bayer/Onyx. Toni K. Choueiri reports institutional funding from Bristol-Myers Squibb, Exelixis, GlaxoSmithKline, Merck, Novartis, Roche, AstraZeneca, Peloton, Pfizer, and TRACON Pharmaceuticals and reports serving on advisory boards for Bayer, GlaxoSmithKline, Merck, AstraZeneca, Prometheus, Novartis, and Pfizer.
All Science Journal Classification (ASJC) codes
- Cancer Research