Investigators of a phase 2 study comparing 2 dosing schedules of sunitinib (Sutent) as first-line therapy for patients with advanced renal cell carcinoma (RCC) concluded that clinicians should stay with the currently approved dosing regimen of 50 mg daily for 4 weeks followed by a 2-week break. Robert Motzer, MD, attending physician, Memorial Sloan-Kettering Cancer Center, New York, who presented the findings, said the data add to a growing body of evidence favoring the dosing regimen that the US Food and Drug Administration approved for sunitinib.
From January 2007 to June 2008, Motzer and colleagues recruited 292 patients (median age, 62 years) with locally recurrent or metastatic RCC of clear cell histology to participate in the phase 2 Renal EFFECT trial. Patients were assigned randomly to receive the conventional 50-mg dose, 4 weeks on/ 2-weeks off (4/2) regimen of sunitinib or a 37.5-mg continuous daily dose (CDD). Treatment continued for up to 2 years, with patients who experienced disease progression or unacceptable toxicity discontinuing earlier. The study’s primary end point was time to tumor progression (TTP), with secondary end points of overall response rate (ORR), overall survival (OS), time to deterioration, and adverse events.
Patients in the 4/2 group received a median of 5 months of treatment compared with 6 months in the CDD arm. On the primary end point of TTP, Motzer said, “There wasn’t a statistically significant difference be tween the 2 arms, but there was a strong trend favoring the 4/2 schedule over continuous dosing.”
Median TTP was 9.9 months for patients treated with the 4/2 regimen compared with 7.1 months for those assigned to the CDD schedule (hazard ratio, 0.77; 95% confidence interval, 0.57-1.04; P = .090). ORR and OS were similar between the study arms. ORR in the 4/2 arm was 32.2% versus 28.1% in the CDD group (P = .044) and OS reached a median of 23.1 months in the 4/2 group compared with 23.5 months in the CDD arm. Time to deterioration and death were significantly improved with the 4/2 schedule versus the CDD regimen (4.0 months vs 2.9 months; P = .034).
No statistically significant difference was observed between the groups in the proportion of patients experiencing all-grade or grade 3/4 adverse events (P >.05). The most common drug-related adverse events overall were fatigue, nausea, diarrhea, dysgeusia, and vomiting (Figure). Hand-foot syndrome was the most frequent grade 3/4 adverse event, observed in 10% of patients in each arm.
Motzer told The Oncology Nurse- APN/PA that patient-reported outcomes suggested the regimens had an equal effect on quality of life and kidney cancer symptoms, but patients on the 4/2 schedule reported better quality of life during the 2 weeks off therapy. “I think this is important in counseling patients on the 4/2 schedule,” Motzer said.
Although previous studies comparing these regimens have found them equally active, Motzer said those studies generally excluded patients with a poor performance score. This study allowed patients with a Karnofsky performance score as low as 70% and enrolled fewer patients (~80%) who had a nephrectomy. Based on these data, Motzer concluded, “The treatment goal, therefore, should be to adhere to the approved dose and schedule.”
Motzer disclosed that funding for the study was provided by Pfizer and he has received compensation from Pfizer
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