Dose Intensity in Real-World Patients With Metastatic Renal Cell Carcinoma Taking Vascular Endothelial Growth Factor...

Tyrosine kinase inhibitors (TKIs) that target the vascular endothelial growth factor receptor (VEGFR) are oral therapies used to treat metastatic renal cell carcinoma (mRCC). VEGFR TKI treatment is often complicated by dose-limiting adverse events (AE). We sought to describe dose intensity and clinical outcomes in a real-world cohort of patients treated with VEGFR TKIs to better characterize dosing patterns and toxicity management compared with previously reported clinical trials.

We conducted a retrospective chart review of sequential patients with mRCC treated with VEGFR TKIs at 1 academic medical center from 2014 to 2021.

139 patients (75% male, 75% white, median age 63 years) were treated with 185 VEGFR TKIs in our real-world cohort. Per International Metastatic RCC Database Consortium criteria, 24% had good risk, 54% intermediate risk, and 22% poor risk mRCC. With their first VEGFR TKI, median relative dose intensity (RDI) was 79%. 52% of patients required a dose reduction, 11% discontinued treatment due to AEs, 15% visited the ED, and 13% were hospitalized for treatment-related adverse events. Cabozantinib had the highest rate of dose reductions (72%) but a low rate of discontinuation (7%). Real-world patients consistently had lower RDI than reported clinical trials with more frequent dose reductions, fewer drug discontinuations, shorter progression-free survival, and shorter overall survival.

Real-world patients were less able to tolerate VEGFR TKIs compared to patients treated on clinical trials. Low real-world RDI, high dose reductions, and low overall discontinuation rates can inform patient counseling prior to treatment initiation and during therapy.