November 2016, Vol. 5, No. 9
Encouraging Outcome with Adjuvant Sunitinib in Renal Cell Carcinoma
For the first time, a randomized study showed that adjuvant therapy improved outcomes in renal cell carcinoma (RCC). Adjuvant sunitinib improved disease-free survival (DFS) by more than 1 year in high-risk locoregional RCC following nephrectomy. Although this is encouraging news, some experts are not ready to adopt this as a new standard of care due to toxicity and lack of an overall survival benefit.
“We have no standard adjuvant treatments for clear cell renal cell carcinoma. These are the first positive data in the adjuvant setting. Sunitinib is a potential new option for adjuvant therapy in renal cell carcinoma given the increase in disease-free survival and the manageable safety profile. The results of this trial could change practice because there is currently no standard treatment in this setting,” said lead author Alain Ravaud, MD, PhD, Bordeaux University Hospital, France.
Dr Ravaud presented the results from the S-TRAC trial at the European Society for Medical Oncology 2016 Congress, and results were published online to coincide with his presentation (N Engl J Med. 2016. DOI: 10.1056/NEJMoa1611406).
“The results of S-TRAC apply only to the patient population enrolled in the trial: clear cell, high-risk RCC without metastases, and sunitinib should be given at a starting dose of 50 mg and dose reductions to 37.5 mg/day as was done in this study. This is important because [adjuvant] sunitinib was not beneficial in the ASSURE trial using a different schedule,” he noted.
S-TRAC randomized 309 patients to recieve sunitinib and 306 to receive placebo. Only high-risk patients were included, and no evidence of metastasis was allowed. They were started on a schedule of 50 mg/day oral sunitinib 4 weeks on, 2 weeks off or on placebo for the same schedule and treated for 1 year or until unacceptable toxicity or disease progression. Dose reductions were allowed to a minimum of 37.5 mg/day.
DFS with sunitinb was 6.8 years versus 5.6 years with placebo, according to a blinded independent review, for a 24% improvement favoring sunitinib (P = .030). Three-year DFS was 64.9% in the sunitinib group versus 59.5% in the placebo group. Five-year DFS was 59.3% for sunitinib versus 51.3% for placebo, an absolute difference of 8%, showing that the effect of treatment is sustained over time, Dr Ravaud said.
There was no difference in overall survival.
The toxicity of sunitinib led to more patients discontinuing the drug: 44% versus 30% for placebo. Reasons for discontinuation were adverse events for 27.5% of sunitinib patients versus 5.3% of placebo patients. The most common adverse events leading to discontinuation were hand-foot syndrome and hypertension. The rate of discontinuations due to progressive disease was 7.2% versus 19.4%, respectively. The rate of serious adverse events (grade ≥3) was 63.4% in the sunitinib arm and 21.7% in the placebo arm.
According to patient-reported outcomes on the EORTC-QLQ-C30 and the EQ-5 questionnaires, quality of life deteriorated on subscales for diarrhea and appetite loss for those taking sunitinib.
S-TRAC was funded by Pfizer.
Formal discussant of this trial, Axel Bex, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, said he could not endorse adjuvant sunitinib on the basis of this phase 2 study. “If S–TRAC were practice changing, it would have to show a survival benefit. I believe that S-TRAC provides weak evidence when we assess the value of healthcare, looking at quality of evidence, harms to benefit ratio, patient’s experience on the drug, and cost. To change my mind, I would need to see an overall survival benefit. We await further results from other studies,” he said.
Federal agencies have a long history of finalizing regulatory documents at the end of an administration. If that history repeats itself in 2016, it may mean a new regulatory environment for an industry that includes more than 60,000 genetic testing products and services. The FDA published a detailed proposal for [ Read More ]
The Knudson Two-Hit Hypothesis is the accepted common mechanism for transformation in patients with most familial cancer syndromes. A germline deleterious mutation in a tumor suppressor gene (TSG) increases the risk of developing specific malignancies. The gatekeeper event is loss of heterozygosity (LOH) or loss of expression of normal protein [ Read More ]