Toxicity-driven Sunitinib Dosing Improves Outcomes in RCC
Toxicity-driven dosing of sunitinib improved response rates and survival compared with historical standard dosing among patients with metastatic renal cell carcinoma.
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Toxicity-driven dosing of sunitinib improved response rates and survival compared with historical standard dosing among patients with metastatic renal cell carcinoma (RCC), according to a study to be presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.1
Better outcomes are associated with higher sunitinib exposure. The aim of this study was to determine if individualized toxicity-driven dosing of sunitinib would improve progression-free survival (PFS) compared with standard dosing.
The multicenter phase 2 trial (ClinicalTrials.gov Identifier: NCT01499121) enrolled 117 patients with metastatic RCC to receive 50 mg per day of sunitinib for 28 days with treatment breaks of 7 days.
Patients who developed grade 2 toxicity prior to the completion of the first cycle remained taking 50 mg per day during the next cycle. Patients who were unable to tolerate 50 mg received a dose reduction to 37.5 mg then 25 mg for at least 7 days. Patients who experienced minimum toxicity during the 28 days received dose escalation to 62.5 mg, then 75 mg during the next cycle.
Dose escalation occurred among 18.5% of patients, with 12 patients receiving 62.5 mg and 8 patients receiving 75 mg. Dose reduction occurred in 45.4% of patients. The dose was reduced to 37.5 mg in 20.4% of patients and to 25 mg in 9.3% of patients. Toxicity resulted in sunitinib discontinuation in 9.3% of patients.
The overall response rate (ORR) was 90.7%, with complete response occurring in 2.8% of patients, partial response in 47.2%, and stable disease in 40.7%. The median progression-free survival (PFS) was 11.9 months (95% CI, 9.3-16.5 months) and the median overall survival (OS) was 35.9 months (95% CI, 27.4 months-not reached).
According to the authors, historical data from the EFFECT trial, which used a 4 week on, 2 week off dosing schedule, demonstrated an ORR of 75%, with complete response, partial response, and stable disease rates of 0%, 32%, and 43%, respectively. The median PFS was 8.5 months (95% CI, 6.9-11.1 months) and the median OS was 23.1 months (95% CI, 17.4-25.4 months).
According to the investigators, these results suggest that “individualized dosing is safe and feasible in a multicenter setting and associated with improved dose intensity and one of the best ORR, PFS, and OS reported for a [tyrosine kinase inhibitor].”
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- Bjarnason GA, Knox JJ, Kollmannsberger CK, et al. Phase II study of individualized sunitinib (SUN) as first-line therapy for metastatic renal cell carcinoma. J Clin Oncol. 2017;35(suppl; abstr 4514).