Copenhagen, Denmark—For the first time, a randomized clinical trial has shown that adjuvant therapy improves outcomes in patients with clear-cell renal-cell carcinoma (RCC). Adjuvant treatment with sunitinib (Sutent) improved disease-free survival (DFS) by >1 year in patients with high-risk locoregional RCC after nephrectomy, according to results from the S-TRAC clinical trial. Although this is encouraging news, at the 2016 European Society for Medical Oncology Congress some experts noted they were not ready to adopt it as a new standard of care, because of the associated 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 investigator Alain Ravaud, MD, PhD, Department of Medical Oncology, Bordeaux University Hospital, France.
“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 daily as was done in this study. This is important, because [adjuvant] sunitinib was not beneficial in the ASSURE trial using a different schedule,” Dr Ravaud emphasized. The study was simultaneously published online (Ravaud A, et al. N Engl J Med. 2016 Oct 10. Epub ahead of print).
The S-TRAC study randomized 309 patients to sunitinib and 306 patients to placebo. Only high-risk patients were included in this study, and no evidence of metastatic disease after nephrectomy or renal metastasis was allowed. Patients received oral sunitinib 50 mg daily for 4 weeks, then 2 weeks without the drug, for 1 year or until unacceptable toxicity or disease progression. Dose reductions were allowed to a minimum of 37.5 mg daily. Patients receiving placebo followed the same schedule.
The median DFS was 6.8 years with sunitinib versus 5.6 years with placebo, according to a blinded independent review, for a 24% improvement favoring sunitinib (P = .030). At 3 years, DFS was 64.9% in the sunitinib group versus 59.5% in the placebo group. At 5 years, the DFS was 59.3% with sunitinib versus 51.3% with placebo, an absolute difference of 8%, indicating that the effect of treatment is sustained over time, Dr Ravaud said. There was no difference in overall survival.
Overall, 44% of patients in the sunitinib group discontinued treatment compared with 30% of patients in the placebo group. Treatment discontinuation because of adverse events was reported in 27.5% of patients in the sunitinib group versus 5.3% of patients in the placebo group.
The most common adverse events leading to treatment discontinuation with sunitinib included hand-foot syndrome and hypertension. The rate of discontinuations caused by progressive disease was 7.2% in the sunitinib group versus 19.4% in the placebo group. The rate of serious (grade ≥3) adverse events was 63.4% in the sunitinib group versus 21.7% in the placebo group.
According to patient-reported outcomes using 2 quality-of-life questionnaires (EORTC QLQ-C30 and EuroQol), the quality of life deteriorated for patients using sunitinib on subscales for diarrhea and appetite loss.
Axel Bex, MD, PhD, of The Netherlands Cancer Institute, Amsterdam, and formal discussant of this study, 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, patients’ 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,” Dr Bex said.
