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(continued on page 137) Kidney Cancer Journal 135 ease-free vs 59.5% in the placebo group. At 5 years, 59.3% were disease-free in the sunitinib group vs 51.3% in the placebo group. Overall survival data were not yet complete. Adverse events were responsible for dose reductions in 34.3% of the sunitinib group compared with only 2% of placebo patients. There were more treatment interruptions as well (46.4% vs 13.2%) and more treatment discontinuations (28.1% vs 5.6%). Despite a similar number of serious adverse events, there were significantly more frequent grade 3/4 adverse events in the sunitinib group vs the placebo group (48.4%/15.8% vs 12.1%/3.6%). The study randomized 615 patients with clear cell RCC to receive sunitinib (n = 309) or placebo (n = 306). Patient characteristics were well balanced between the arms. The median age of patients in the sunitinib arm was 57 years, and most were males (71.8%). Most patients had an ECOG performance score of 0 (73.8%). Overall, 90.6% of those in the sunitinib arm had a stage 3 tumor, with no nodal involvement and no metastasis. Of these patients, 37.2% were considered low-risk (any Fuhrman grade and ECOG score of 0 or Fuhrman grade 1 and ECOG score of ≥1) and 53.4% were high-risk (Fuhrman grade ≥2 and ECOG score of ≥1). The remainder of the patients had either stage T4 tumors or had locoregional nodal involvement. Sunitinib was administered at 50 mg daily for 4 weeks followed by 2 weeks without treatment. One dose reduction was allowed in the study, to 37.5 mg per day. Overall, more than half of patients (54.2%) were able to maintain treatment with the starting dose of 50 mg per day. The median daily dose was 45.9 mg. Treatment-emergent AEs were experienced by 99.7% of patients treated with sunitinib versus 88.5% in the placebo arm. Treatment-emergent AEs by investigator assessment occurred in 98.4% of those treated with sunitinib versus 75.7% with placebo. AEs led to discontinuation for 28.1% of patients in the sunitinib arm versus 5.6% of those in the placebo group. The most common AEs in the sunitinib arm were diarrhea (56.9%), palmar–plantar erythrodysesthesia (50.3%), hypertension (36.9%), fatigue (36.9%), and nausea (34.3%). The most common grade 3/4 AEs were palmar–plantar erythrodysesthesia (16%), neutropenia (8.5%), hypertension (7.8%), and thrombocytopenia (6.2%). The rate of serious adverse events AEs was similar for sunitinib (21.9%) versus placebo (17.1%). Results from the ASSURE Trial In the phase 3 ASSURE trial neither sunitinib nor sorafenib (Nexavar) improved outcomes when administered after surgery to patients with locally advanced RCC. The trial enrolled patients with non-clear cell histology (21%), those at intermediate risk (50%), and patients with less than stage 3 disease (34%). Additionally, the starting daily I N T E R V I E W Inside the Clinical Trials on Adjuvant Therapy and Re-examining Its Risk/Benefit Ratio This interview was conducted with Allan J. Pantuck, MD, one of the authors of a study recently published in the New England Journal of Medicine, and Alexandra Drakaki, MD, PhD, on the use of adjuvant sunitinib in high-risk renal cell carcinoma after nephrectomy. A leading investigator on numerous clinical trials, Dr Pantuck is Professor of Urology at the UCLA Department of Urology, Los Angeles, California. Dr Pantuck’s research programs focus on gene and immune therapies for genitourinary cancer, molecular and genomic characterization of kidney cancer, and nutritional chemoprevention of prostate cancer. Dr. Drakaki is an Assistant Professor of Medicine (Hematolgy/ Oncology) and Urology and the Medical Director of the GU Oncology Program at the Institute of Urologic Oncology at UCLA. Dr. Drakaki is the principal investigator of pivotal genitourinary clinical trials. Her research focus is on the role of non-coding RNAs in GU malignancies and identification of novel drugs that will be used from the bench to the bedside. Q. Please define the importance of adjuvant therapy in kidney cancer and delineate the efforts so far to make progress in this area. Dr Drakaki: There are a number of major issues. The most important to consider is that an effective adjuvant treatment is one of the “Holy Grails,” not just for kidney cancer, but in all of oncology. There are relatively few cancer sites, such as lung, breast, colon or melanoma, where adjuvant therapies have proven to be effective. 16% of all RCC cases are loco-regional at the time of diagnosis, and depending on their clinical and pathologic features, up to 40% of these patients will ultimately relapse and develop metastatic disease after surgery. Investigators have been attempting to find an effective adjuvant therapy in kidney cancer for decades, going all the way back to the time when interleukin-2, interferon and hormonal therapies were considered the primary options of treatment; however none of these therapies, even when effective in the metastatic setting, proved to be effective in preventing relapse after primary treatment. Q. How would you characterize the latest results from the S-TRAC (Sunitinib Treatment Of Renal Adjuvant Cancer) trial as compared with other data recently published? (continued on next page)


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