Background: VEGF targeted therapy (VEGF-TT) are standard in advanced metastatic renal cell carcinoma (mRCC), however, toxicities that can lead to drug discontinuation can have a significant impact on patient (pt) outcomes. We aimed to identify risk factors for toxicity and develop the first model to predict toxicity-related treatment discontinuation (TrRD) in mRCC pts treated with VEGF-TT. Methods: Baseline characteristics and treatment outcome data were collected on 936 mRCC pts on first-line VEGF-TT from 7 IMDC institutions. TrTD was analyzed using a competing risk regression model for treatment discontinuation. Results: Median follow up was 23 months. Treatment discontinuation occurred in 833 pts (89%), of which 198 (23.8%) were related to drug toxicity. Sunitinib was the most common VEGF-TT (77%) in our series followed by sorafenib (18.4%). Median time on therapy was 7.1 months in all pts and 4.4 months for pts with TrTD. Most common toxicities leading to TrTD included fatigue, diarrhea and mucositis. On multivariate analysis, significant adverse predictors for TrTD (p<0.05) were: age (≥60 years), baseline glomerular filtration rate (GFR) <30 cc/min, number of metastatic sites (>1), and baseline sodium level (<LLN). A model was developed using the number of patient risk factors to predict the risk of TrTD (Table). Conclusions: In the largest series reported to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors that predict toxicity-related treatment discontinuation in mRCC pts treated with VEGF-TT. Based on the number of risk factors present, we built the first model to predict treatment-related drug discontinuation. This model can be used for treatment and frequency of monitoring considerations in clinical practice.

Risk groups were derived based on number of risk factors (RF).* The RF is 1 for age ≥60 and is 2 for age≥70.