1. In patients with locoregional clear-cell renal cell carcinoma (RCC) at high risk of recurrence post nephrectomy, those taking sunitinib had a significantly longer median disease-free survival compared to those in the placebo group.
2. The rate of adverse events were greater in patients who took sunitinib compared to those taking placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The prognosis of RCC is dependent on stage. Individuals with locoregional disease (stage 3) have high rates of relapse after nephrectomy. There is currently no curative treatment for such patients, and adjuvant therapies are used to help decrease the rate of relapse. One such therapy showing proven efficacy is antiangiogenic drugs, such as the vascular endothelial growth factor (VEGF) pathway inhibitor sunitinib in patients with metastatic RCC. In this randomized, double blind, phase 3 trial, sunitinib was compared to placebo for adjuvant treatment for patients at high risk of recurrence of RCC following nephrectomy. The sunitinib group had a significantly longer median disease free survival compared to the placebo group. However, a greater rate of adverse events occurred in the sunitinib group which resulted in dose reductions, dose interruptions and discontinuations compared to the placebo group. The major strength of this trial was its double blind, randomized controlled methodology.
Click to read the study, published in NEJM
In-Depth [randomized controlled trial]: This was a randomized, double-blind, phase 3 trial involving 99 centers in 21 countries enrolled 615 patients, to receive either sunitinib (50 mg/day) or placebo. The primary endpoint was disease-free survival, and secondary endpoints were overall survival and safety.
A total of 615 patients were enrolled in the study. From these patients, 306 received sunitinib and 304 received placebo. The median disease free survival was 6.8 years (95%CI 5.8-not reached) in the sunitinib group, and 5.6 years (95%CI 3.6-6.6) in the placebo group (HR 0.75; 95%CI 0.59 – 0.98; p = 0.03). Treatment-emergent adverse events occurred in 99.7% receiving sunitinib, and 88.5% of patients receiving placebo. The most common adverse events in the sunitinib group were diarrhea, palmar-plantar erythrodysesthesia, hypertension, fatigue and nausea. Dose reductions or interruptions due to adverse events occurred in 34.3% and 46.4%, respectively, in those taking sunitinib, and 2% and 13.2% in the placebo group. Treatment discontinuations due to adverse events occurred in 86 patients (26.1%) in the sunitinib group, and 17 patients (5.6%) in the placebo group. No deaths were the result of toxic effects.
Image: PD
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