Administering sunitinib on a 2 weeks on, 1 week off (2/1) schedule does not decrease the rate of grade 3 toxicity — but may improve other clinical outcomes — among patients with metastatic renal cell carcinoma (RCC), according to a study published in the Journal of Clinical Oncology.1
The standard sunitinib schedule in the metastatic RCC setting is 4 weeks on and 2 weeks off (4/2). This schedule is, however, associated with adverse events (AEs) including grade 3 to 4 fatigue, hand-foot syndrome (HFS), and diarrhea. Reducing the incidence of these AEs may prevent dose interruptions/reductions and improve quality of life (QoL).
For this phase 2 study (ClinicalTrials.gov Identifier: NCT02060370), researchers evaluated the safety and efficacy of sunitinib 50 mg administered on a 2/1 schedule among 59 patients with metastatic RCC. Patients were able to adjust dose and schedule depending on AEs. The Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire was completed at baseline and at weeks 12, 24, and 36 for QoL assessment.
After a median follow-up of 17 months, 25% of patients developed grade 3 fatigue, HFS, or diarrhea (95% CI, 15.0%-38.4%), with a median time to development of 3.8 months. Thirty-seven percent of patients required a dose reduction, and 10% discontinued treatment because of toxicity.
The overall response rate was 56% (95% CI, 42.4%-68.8%), with a 2% complete response rate and a 54% partial response rate. Twelve percent of patients had progressive disease as best response. The median progression-free survival was 13.7 months (95% CI, 10.9-16.3) and median overall survival (OS) was not reached.
A drop of 0% to 10% from baseline in FACT-G scores was noted after 12 weeks, though patients who continued treatment for at least 36 weeks showed the smallest decline in QoL.
The authors concluded that the “primary end point of decreased grade 3 toxicity was not met; however, treatment with a 2/1 sunitinib schedule is associated with a lack of grade 4 toxicity, a low patient discontinuation rate, and high efficacy.”
- Jonasch E, Slack RS, Geynisman DM, et al. Phase II study of two weeks on, one week off sunitinib scheduling in patients with metastatic renal cell carcinoma. J Clin Oncol. 2018 Apr 11. doi: 10.1200/JCO.2017.77.1485 [Epub ahead of print]