The FDA’s Oncologic Drug Advisory Committee today voted 6-6 on whether the risk-benefit profile of sunitinib malate is acceptable for the adjuvant treatment of patients with a high-risk for recurrent renal cell carcinoma following nephrectomy.
The committee considered data from the S-TRAC trial, which randomly assigned patients at high risk for recurrent renal cell carcinoma following nephrectomy to 1 year of sunitinib (Sutent, Pfizer Oncology; n = 309) or placebo (n = 306). Patients assigned sunitinib received 50-mg doses for 4 weeks following by 2 weeks off, and the dose could be reduced to 37.5 mg.
DFS served as the study’s primary endpoint.
After 257 events — 113 of which occurred in the sunitinib arm and 144 in the placebo arm — median DFS was 6.8 years in the sunitinib arm and 5.6 years in the placebo arm (HR = 0.76; 95% CI, 0.59-0.97).
Adverse events associated with sunitinib appeared comparable to those observed in patients with metastatic renal cell carcinoma. Twenty-eight percent of patients assigned sunitinib and 5% assigned placebo permanently discontinued treatment due to toxicity.
More patients assigned sunitinib experienced dose reductions or delays (46% vs. 35%) and grade 3 to grade 4 adverse events (60% vs. 15%).
Results of an OS analysis — conducted in Jan. 2017, with a final analysis expected in 2019 — showed an HR of 0.92 (95% CI, 0.66-1.28).
Some committee members questioned the validity of DFS as a valid surrogate endpoint for adjuvant treatment of kidney cancer, whereas others questioned whether the data showed a true benefit.
“The signal wasn’t very clear, and I struggled with the robustness of the data,” Susan Halabi, PhD, professor in the department of biostatistics and bioinformatics at Duke University Medical Center, who voted against approval, said during the meeting. “I have no issues using DFS as a primary endpoint, because it has been extensively studied in the adjuvant setting [in other diseases.] But [I am not sure about] basing an approval on 257 events with the confidence interval almost touching 1.”
Lance C. Pagliaro, MD, professor of oncology at Mayo Clinic in Rochester, Minnesota, also casted a dissenting vote.
“It’s a year of sunitinib now to avoid a year of sunitinib later,” he said. “I don’t see the net benefit in terms of burden and the number of patient-years to get treatment to [achieve] the same end result.” – by Alexandra Todak