ESMO 2016

Longer disease-free survival in phase III trial of sunitinib as adjuvant treatment for kidney cancer

Dr Alain Ravaud - Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

The S-TRAC study is a study testing sunitinib in adjuvant high-risk patients with renal cell carcinoma. Sunitinib is already a very active drug in metastatic renal cell carcinoma and is a standard in first line but there is no data to show any improvement in the adjuvant setting with already used drugs. So the study was designed for renal cell carcinoma patients but the specific feature which is clear cell, the more frequent one. The patients were stratified by risk and only patients with a high risk of recurrence were included in the study and randomisation was done with a standard arm that was placebo and the experimental arm that was sunitinib. The dosage of sunitinib and the schedule was the same as used in the metastatic setting: 15mg/day orally, four weeks on, two weeks off. 600 patients were planned and 615 were included.

These are the characteristics of the patients, they are well-balanced. The main points are that the performance status of the patients were quite good, as you can see it’s close to 75% of the patients are ECOG PS 0 and 25% had ECOG 1. It was clearly clear cell predominant and the risks were only high risk so you can’t separate different risks which are what we call low risk of the T3 that are 37% in each arm, the T3 highs that are more than 50% and the very more aggressive disease, T4N0 so any TN positive which are only around 10%.

Here are the results of the primary endpoint which is a disease free survival blind independent central review. As you can see, there is significant gain in the median survival, with placebo 5.6 years and the sunitinib which is 6.8 years with a p-value of 0.03. What is important is that you can see that the curves diverge very early and it’s maintained over time and that could be seen with a hazard ratio of 0.761 which means that these data are significant.

You may have also that you could look at the rate opposite time and the three year DFS rate was 59.5% in the placebo arm and 64.9% in the study arm, so 5.4% of difference. If you go later, at five years, this rate came from 51.3% to 59.3% which is 8% of difference.

Patients experienced adverse events as well as in the sunitinib arm as well as in the placebo arm. In fact there were more grade 3 in the sunitinib arm than in the placebo, 60% compared to 20%, but if we go to serious adverse events the numbers and percentage were quite similar, as you can see, around 20% in both arms. If we look only to the sunitinib arm the major cause for serious adverse events were hypertension and thrombocytopenia.

So, in conclusion, adjuvant treatment with sunitinib prolonged disease free survival in patients with high risk local regional clear cell carcinoma; it was the primary endpoint. The second point which is very important, the effect of this one year adjuvant treatment is sustained over time so more sunitinib treated patients were even free at three years and five years. The safety profile of adjuvant sunitinib was acceptable and consistent with the broad treatment experiment for this drug in metastatic RCC, no signs of different side effects, and we think that these results represent a major step forward in the clinical management of clear cell RCC.