For adults with metastatic, treatment-naive renal clear cell carcinoma, an alternate (2 weeks on, 1 week off) oral sunitinib schedule might be more tolerable than the approved 4:2 schedule, according to the results of a single-arm, multicenter, phase 2 trial.
After a median follow-up of 17 months, 25% of 59 patients had experienced grade 3 fatigue, hand-foot syndrome, or diarrhea, 37% had required dose reductions, and only 10% had stopped treatment because of toxicity. Rates of treatment discontinuation and dose reduction compared favorably with those seen with the 4:2 schedule in the pivotal COMPARZ (Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma) trial (37% and 51%, respectively), reported Eric Jonasch, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his associates in the Journal of Clinical Oncology.
Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, is standard first-line therapy for metastatic clear cell renal cell carcinoma. But side effects impede treatment, and moderate to severe diarrhea, fatigue, and hand-foot syndrome are especially hard to manage without dose-reducing or interrupting therapy. These and other toxicities tend to peak during the second half of the Food and Drug Administration–approved 4-week treatment cycle, the investigators noted. Building on retrospective studies that have reported less toxicity with an alternate 2:1 schedule, they powered their trial to test whether this schedule would produce grade 3 or worse diarrhea, fatigue, or hand-foot syndrome in no more than 15% of patients.
Despite missing this endpoint, “the initial 2:1 schedule and subsequent schedule and dose alterations ensured that 90% [of patients] could continue treatment and avoid protracted high-grade toxicities,” the investigators said. Sunitinib showed “robust” efficacy – a 57% overall response rate and 13.7-month median progression-free survival – even though most patients were intermediate risk (67%) or poor risk (10%), they added. The nonrandomized data support using the alternate 2:1 schedule to maintain quality of life and extend treatment duration, they concluded.
Pfizer makes sunitinib and funded the study. Dr. Jonasch disclosed research funding, travel reimbursement, and an advisory relationship with Pfizer.
SOURCE: Jonasch E et al. J Clin Oncol. 2018 Apr 11. doi: 10.1200/JCO.2017.77.1485.