Phase III Study of Sunitinib Is First to Show Benefit in Adjuvant Setting for Treatment of Renal Cell Carcinoma

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Sunitinib (Sutent) improved disease-free survival by more than 1 year when used as adjuvant treatment for high-risk locoregional renal cell carcinoma following nephrectomy, but with the cost of toxicity. S-TRAC is the first phase III trial showing a benefit for adjuvant therapy in renal cell carcinoma. These results were reported at the 2016 European Society for Medical Oncology (ESMO) Congress1 and published simultaneously online in The New England Journal of Medicine.2

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.
— Alain Ravaud, MD

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“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, if approved by health authorities, because there is currently no standard treatment in this setting,” said lead author Alain Ravaud, MD, of the Hôpital Saint-André, Bordeaux, France.

Dr. Ravaud cautioned that the results apply to only the patient population enrolled in the trial—clear-cell, high-risk renal cell carcinoma without metastases—and that it should be given at a starting dose of 50 mg and dose reductions to 37.5 mg/d, as was done in this study. “This is important because [adjuvant] sunitinib was not beneficial in the ASSURE trial using a different method,” he noted. (See the discussant’s comments on the ASSURE trial, below.)

About 16% of all cases of renal cell carcinoma are diagnosed with locoregional disease, and of them, up to 49% have a relapse with metastasis after nephrectomy. “The recurrence rate following nephrectomy distinguishes kidney cancer from other tumors such as breast cancer, where in general there is a low chance of it coming back,” Dr. Ravaud explained. Thus, there is a rationale for adjuvant therapy,” he added.

Study Details

The S-TRAC study randomized 309 patients to receive sunitinib and 306 patients to receive placebo. Only high-risk patients were included, and no evidence of metastasis was allowed. They were started on 50 mg/d of sunitinib orally 4 weeks on/2 weeks off or on placebo for the same schedule. Dose reductions were allowed to a minimum of 37.5 mg/d. Treatment was for 1 year or until recurrence, second cancer, or consent withdrawal.

At baseline, the treatment arms were well balanced for demographic and disease characteristics. According to the University of California Los Angeles Integrated Staging System, 37% had stage T3 low-risk disease, more than 50% had T3 high-risk disease, and 10% had stage T4 or more locally advanced disease. Median age was 57 years, and the majority were men.

Survival Outcomes

Sunitinib extended disease-free survival to 6.8 years vs 5.6 years with placebo, according to a blinded independent review, representing a significant 24% improvement favoring sunitinib (P = .030). Three-year disease-free survival was 64.9% in the sunitinib group vs 59.5% in the placebo group. Five-year disease-free survival was 59.3% for sunitinib vs 51.3% for placebo, reflecting an 8% difference at that time point. “The effect of 1 year of treatment is sustained over time, with more sunitinib patients event-free at 3 years and 5 years vs placebo,” Dr. Ravaud emphasized.

Adjuvant Therapy for Renal Cell Carcinoma

  • Adjuvant therapy with sunitinib extended disease-free survival by more than 1 year in patients with renal cell carcinoma following nephrectomy.
  • Treatment with sunitinib led to more toxicity, treatment discontinuation, and some decrements in quality of life.
  • This is the first trial to show an advantage for a treatment in the adjuvant setting in renal cell carcinoma, but the jury is out until there are more data, particularly a survival benefit to balance the toxicity.

Overall survival data are not mature.

In a subgroup analysis of patients at higher risk than the overall population (tumor stage 3, grade 2 or higher, ECOG [Eastern Cooperative Oncology Group] score of 1 or higher, or tumor stage 4), the difference in disease-free survival was significant up to 2.2 years, on the basis of independent central review (P = .04).


The rates of treatment discontinuation and reasons for it reflect the tolerability of sunitinib. Treatment was completed by 56% patients in the sunitinib arm vs 69% of patients in the placebo arm. Treatment discontinuation rates were 44% vs 30%, respectively. Reasons for discontinuation were adverse events for 27.5% of sunitinib patients vs 5.3% of placebo patients. The most common adverse events leading to treatment discontinuation were hand-foot syndrome and hypertension. The rate of treatment discontinuation due to progressive disease was 7.2% vs 19.4%, respectively.

Any treatment-related adverse event was reported by 99.7% of the sunitinib arm and 88.5% of the placebo arm. Adverse events that investigators attributed to treatment occurred in 98.4% and 75.7%, respectively. The rate of serious adverse events (grade 3 or higher) was 63.4% in the sunitinib arm and 21.7% in the placebo arm.

Quality of life was assessed by the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC-QLQ-C30) and the European Quality of Life-5 Dimensions (EQ-5). Quality of life deteriorated for the sunitinib-treated patients on subscales for diarrhea and appetite loss, according to patient-reported outcomes.

For more on the use of sunitinib in renal cell carcinoma (compared with cabozantinib) read here. ■

Disclosure: The S-TRAC trial was funded by Pfizer. Dr. Ravaud is a member of the advisory board in renal cell carcinoma for Pfizer, Novartis, GlaxoSmithKline, Roche, and Bristol-Myers Squibb; has received institutional support grants from Pfizer and Novartis; and has received travel expenses from Pfizer, Novartis, and Bristol-Myers Squibb.


1. Ravaud A, Motzer RJ, Pandha HS, et al: Phase III trial of sunitinib vs placebo as adjuvant treatment for high-risk renal cell carcinoma after nephrectomy (S-TRAC). 2016 ESMO Congress. Abstract LBA11_PR. Presented October 10, 2016.

2. Ravaud A, Motzer RJ, Pandha HS, et al: Adjuvant sunitinib in high-risk, renal-cell carcinoma after nephrectomy. N Engl J Med. October 9, 2016 (early release online).

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Expert Point of View: Axel Bex, MD, PhD

S-TRAC provides weak evidence when we assess the value of health care, looking at quality of evidence, harms-to-benefit ratio, patient’s values and preferences, and cost. To change my mind, I would need to see an overall survival benefit.
— Axel Bex, MD, PhD

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