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;122:411-9.

Cellular effects induced by 17-β-estradiol to reduce the survival of renal cell carcinoma cells

“…However, diverse genetic alterations are linked to renal cancer progression and to our ability to predict its risk [ 13 , 23 ]. Targeted therapies incorporating inhibitors of the vascular endothelial growth factor (VEGF) pathway is the major treatment for patients with metastatic RCC [ 18 , 20 , 49 ]. For example, anti-angiogenic drugs such as sunitinib can nullify alterations in the microvascular properties of some human cancers [ 35 ].…”

Outcomes based on age in patients with metastatic renal cell carcinoma treated with first line targeted therapy or checkpoint immunotherapy: Older patients more prone to toxicity

“…On the other hand, frequency and severity of major toxic events leading to dose reductions and discontinuations differ according to patient age [3,13]. A study [26] from the International Metastatic Renal Cell Cancer database identified older age to be a predictive factor of toxicity-related discontinuations of treatment among patients treated with targeted therapeutic agents. Likewise, Miyake et al [27] found that the proportion of older patients undergoing a modified sunitinib regimen, whereby the initial dose was reduced due to toxicity, was larger when compared with younger adults.…”

Results of weekday-on and weekend-off administration schedule of sunitinib therapy for advanced renal cell carcinoma

“…Chronic kidney disease was already reported to be significantly associated with toxicity-related treatment discontinuation [22, 23]. Hyponatremia is well-known to be correlated with poor prognosis in RCC patients treated with molecular-targeted therapy [24–26].…”

“…In this study, discontinuation of sunitinib therapy was significantly correlated with the presence of hyponatremia and renal impairment. Chronic kidney disease was already reported to be significantly associated with toxicity-related treatment discontinuation [ 22 , 23 ]. Hyponatremia is well-known to be correlated with poor prognosis in RCC patients treated with molecular-targeted therapy [ 24 – 26 ].…”