Eric Singer, MD, discusses the relevant data that led to the approval of sunitinib in the adjuvant treatment setting for renal cell carcinoma.
Eric A. Singer, MD, chief, Division of Urologic Oncology, director, Urologic Oncology Fellowship Program, and co-director, Genitourinary Disease-Specific Research Group at the Ohio State University Comprehensive Cancer Center, and professor, Department of Urology, Division of Bioethic at the Ohio State University College of Medicine, discusses the data that led to the FDA approval of adjuvant sunitinib (Sutent) for patients with high-risk renal cell carcinoma (RCC).
While treatment for kidney cancer and RCC has improved, patients in need of treatment in the adjuvant setting have had a tougher set of choices. However, that landscape has started to change with the addition of tyrosine kinase inhibitors (TKIs) like sunitinib and a renewed focus on immunotherapy. In particular, the randomized, double-blind, phase 3 S-TRAC trial (NCT00375674) showed that sunitinib led to a median duration of disease-free survival of 6.8 years 95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (HR 0.76; 95% CI, 0.59-0.98; P = 0.03). However, the TKI treatment came with many adverse events (AEs), which led to a discontinuation rate of 28.1%, with 48.4% of AEs being grade 3 compared with 12.1% being grade 4.
Still, the therapy was better than the placebo and approved as a means of treatment for a high-risk patient population. Singer discusses the importance of this drug as a first step in understanding better treatments for these patients and why the AEs make it a challenging treatment to recommend.
0:08 | S-TRAC was this trial of using sunitinib vs placebo, and it's interesting to note that placebo is a reasonable alternative therapy to use in some very specific cancer cases, such as this one here, where we don't have an established or standard therapy. So, some people get concerned when they see placebo-controlled trials. I think in the adjuvant space like this with no proven therapy, a placebo was a reasonable comparison arm. [Researchers] looked at 615 patients and looked at their disease-free survival, and they found that there was a benefit [with] about a 24% reduction in recurrence for patients who receive sunitinib versus placebo. That led to the FDA approval of sunitinib in the adjuvant setting.
1:02 | Again...there were a good amount of dose reductions. There was, of course, the expected toxicities with TKIs [and] sunitinib being one of the earliest ones used. And that's given in a 4 week on 2 weeks off dosing schedule, again, because of the toxicities that we can see with that drug. So, encouraging in that we got an approval, but I would say that it's really a rarely used drug, because of the toxicity and just the recurrence free survival benefit. So, it does exist, but I can't say that it's something that I really recommend to patients because of that toxicity profile.