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.
Materials and Methods
We conducted a retrospective chart review of sequential patients with mRCC treated with VEGFR TKIs at one 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 IMDC 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.
Patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors at a single academic medical center were retrospectively reviewed. These 139 real-world patients had high rates of dose reduction (52%) but low rates of drug discontinuation (11%), with lower relative dose intensity than reported in clinical trials.
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Accepted: February 13, 2023
Received in revised form: February 12, 2023
Received: December 21, 2022
Publication stageIn Press Journal Pre-Proof
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