He started by focusing on S-TRAC, the only randomized control trial to demonstrate a benefit to adjuvant therapy. In the updated S-TRAC data, in a central independent review, there was a disease-free survival benefit to use of adjuvant sunitinib over placebo in high-risk patients (HR 0.76, p = 0.03). This translated to a 5-year absolute benefit of approximately 8.0%. He then went on to make an excellent point that this exceeds the absolute benefit of many adjuvant therapies in other malignancies – all of which are standard of care (ie oxaliplatin for colon cancer, docetaxel for breast cancer, Herceptin for breast cancer, ipilimumab for melanoma – all <8% 5-year absolute risk reduction).
He also noted that while S-TRAC did not show a survival benefit, only 25% of events had been recorded – this is immature data and cannot be used in an argument! The KM curves for many other established therapies with only 25% of events recorded look quite similar – but the curves may separate later.
Next, he addressed the side effects of TKI’s – hand-foot syndrome, hypertension, neutropenia, thrombocytopenia. He feels that these are relatively benign, stop with cessation of medication and are manageable – and should not be the reason to not give the drug.
He finished with a survey of patients with RCC, in which they were asked what would be important in their decision making regarding getting a treatment for their RCC. Overwhelmingly, >60% reported that disease free survival (DFS) and overall survival (OS) would be the most important. 43% felt that toxicity and side effects would be important. This is based on KCCure data.
So, toxicity should not drive decision making. DFS benefit has been demonstrated. It is now FDA approved.
CON: Hans Hammers, MD provided the opposite side of this argument.
First, the principle of adjuvant therapy is cure – complete resolution of micrometastatic disease. If it is not curative, it is not appropriate for adjuvant therapy. However, TKI’s are demonstrated to be non-cytotoxic – they merely control the disease. Hence, they cannot be compared to adjuvant chemotherapy agents of other malignancies.
Next, he went on to review the S-TRAC data. Importantly, he noted that while there was DFS benefit in the independent central review, in the investigator review of the data, there was no difference! (HR 0.81, p = 0.077). He again reiterated that there was also no OS benefit yet, even with longer follow-up (Motzer EU 2018).
Ultimately, with 3 negative trials (ASSURE, PROTECT and reportedly ATLAS) and only 1 positive trial – there is some degree of chance, and this may represent a false positive.
As a result, adjuvant sunitinib is not recommended – patients with high-risk localized RCC should be enrolled in clinical trials whenever possible.
Pro: Daniel George, MD
Con: Hans Hammers, MD
Read the First Debate: Active Surveillance for Large Renal Masses is Appropriate
Read the Second Debate: Tumor Enucleation for Sporadic T1 RCC is Oncologically Sound
Read the Fourth Debate: 10 years of Big Data Have Changed Renal Cell Carcinoma Management
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, | twitter: @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA