A reduced starting dose of tyrosine kinase inhibitor (TKI) therapy may provide similar efficacy, but with improved tolerability, compared with a full initial starting dose in patients with metastatic renal cell carcinoma (RCC). These study results were reported in the Journal of Hematology Oncology Pharmacy.

TKIs are often used in treatment of metastatic RCC, but adverse events with these agents can limit patients’ ability to continue treatment. “In clinical trials of patients with metastatic RCC, approximately 46% of patients receiving these targeted agents as monotherapy required dose reductions,” the study investigators explained in their report. They set out to determine the effects of differing TKI starting doses on clinical outcomes in metastatic RCC.

The study was a retrospective chart review of adult patients with metastatic RCC being treated with TKI therapy for metastatic RCC at the Georgia Cancer Center-Laney Walker Campus in Augusta, Georgia. The researchers categorized patients into 2 categories according to the starting TKI dose received. One category included patients receiving the full indicated starting dose of the prescribed TKI (full-dose cohort), while the other category included patients who had received a reduced starting dose (reduced-dose cohort).

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The percentage of patients receiving a reduced initial TKI dose during first-line therapy was the primary outcome of the study. Secondary outcomes related to rates of TKI dose modifications, drug discontinuation, adverse events, and survival in patients treated in the first-line setting.

There were 42 patients included in the study. Among those treated in the first line, there were 14 (33.3%) patients in the full-dose cohort, and 28 (66.7%) in the reduced-dose cohort. In the full-dose cohort 13 patients were prescribed pazopanib for first-line therapy, and 1 patient received sunitinib. In the reduced-dose cohort, pazopanib and sunitinib were each prescribed to 11 patients in the first line, cabozantinib was prescribed to 5 patients, and axitinib was prescribed to 1 patient.

Overall survival time did not significantly differ between dose categories. The mean time to death was 20.1 months in the reduced-dose cohort, and it was 25 months in the full-dose cohort (P =.55). There were 7 patients who died in the reduced-dose cohort and 6 who died in the full-dose cohort (P =.3). Mean treatment durations were 6.6 months (SD, 6.7) in the reduced-dose cohort and 13.9 months (SD, 13) in the full-dose cohort (P =.14).

TKI dose reductions (P =1.00) and discontinuations (P =.30) also occurred at similar rates between the 2 dose categories. Adverse events were the cause for all dose reductions in both cohorts, and were involved in 36.8% of discontinuations in the full-dose cohort and 11.1% of drug discontinuations in the reduced-dose cohort. Disease progression was a reason for discontinuation for 31.6% of patients in the full-dose cohort and 77.8% of patients in the reduced-dose cohort.

“Our findings suggest that starting a TKI at a reduced dose improves medication tolerability, without compromising its efficacy,” the study investigators concluded.


Stitt TM, Saunders KM, Rowling BC, Waller JL, Clemmons AB. Reduced starting dose of tyrosine kinase inhibitors in patients with metastatic renal-cell carcinoma. J Hematol Oncol Pharm. 2022;12(3):138-144.