The most recent adjuvant trials (done in the targeted era) use placebo as a control, and usually assume that 1 year of adjuvant treatment is enough. The ASSURE trial compared Sunitinib to Sorafenib and to placebo. Almost 2000 patients were enrolled, but the trial was negative, showing no benefit to the treatment arms.
The PROTECT study compared adjuvant Pazopanib to placebo with disease free survival (DFS) being the primary endpoint. This study also did not show an overall survival benefit for PAZOPANIB. The S-TRAC trial compared Sunitinib to placebo with more than 600 patients enrolled, with DFS being the primary endpoint. In contrast to ASSURE, this was a positive trial, showing an advantage to the treatment arm with Sunitinib. This resulted in the FDA approving this adjuvant treatment after nephrectomy for M0 RCC patients as of November 2017. However, despite FDA approval, adjuvant Sunitinib remains controversial. There have been high frequencies of treatment discontinuation for toxicity in both Sunitinb studies (ASSURE and S-TRAC) and evidence of decreased quality of life during that year. Additionally, even in S-TRAC there is no definite overall survival benefit. The FDA approval of Sunitinib as standard of care therapy has resulted in the debate of whether we should amend all current and future studies to include Sunitinib arm instead of a placebo arm, with no clear answer.
Currently there are ongoing phase 3 trials assessing the role of other adjuvant therapies – including Atezolizumab, Pembrolizumab, and Nivolumab+Ipilimumab compared to placebo. Dr. Harshman concluded her talk by stating that despite the recent FDA approval, we remain without an adjuvant systemic therapy proven to increase overall survival over surgery alone. We should await data from other maturing TKI/mTOR inhibitor trials. Lastly, due to the controversial nature of this topic, shared decision making with the patient with high risk disease is the recommended therapeutic strategy.
Presented by: Lauren C. Harshman, MD Medical Oncology, Assistant Professor, Medicine, Harvard Medical School, Assistant Professor, Medical Oncology, Dana-Farber Cancer Institute
Written by: Hanan Goldberg, MD @GoldbergHanan Society of Urologic Oncology Fellow University of Toronto, Princess Margaret Cancer Centre at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC