Mace Rothenberg, MD
Sunitinib (Sutent) extended disease-free survival (DFS) versus placebo as an adjuvant therapy for patients with renal cell carcinoma (RCC) at high risk of recurrence in the phase III S-TRAC trial, according to Pfizer, the manufacturer of the multitargeted tyrosine kinase inhibitor (TKI).
The safety profile for sunitinib in the S-TRAC study was consistent with previously reported adverse-event data for the drug. Pfizer plans to submit the full trial data for presentation at the 2016 ESMO Congress in October.
“Sutent has long been a standard of care for the treatment of advanced RCC, and has reached more than 250,000 patients across diagnoses around the world since its initial approval 10 years ago,” Mace Rothenberg, MD, Pfizer’s chief development officer, Oncology, said in a statement. “We believe the results from the S-TRAC trial support the potential for Sutent to be a treatment option in a broader range of patients. We look forward to sharing the detailed results of S-TRAC with the oncology community and discussing these data with health authorities to determine an appropriate regulatory path forward.”
The double-blind phase III S-TRAC trial randomized more than 670 patients at high-risk of RCC recurrence to adjuvant sunitinib or placebo. The study included a global cohort and a China-specific cohort. The primary endpoint of the trial was DFS, which the study defined as the time between randomization and either recurrence, a secondary malignancy, or death.
Earlier this year, results reported from the phase III ASSURE trial1
had not shown a positive outlook for sunitinib in the adjuvant RCC setting. In the study, neither sunitinib nor sorafenib (Nexavar) improved outcomes when administered after surgery to patients with locally advanced RCC.
The median DFS was 5.6 years in both the sorafenib and sunitinib arms and 5.7 years in the placebo arm. The 5-year DFS rate was 52.8% in the sorafenib arm (HR, 0.98; 97.5% CI, 0.81-1.19), 53.8% in the sunitinib arm (HR, 1.01; 97.5% CI, 0.83-1.23), and 55.8% in the placebo arm. In total, there were 272, 265, and 270 DFS events observed in the sorafenib, sunitinib, and placebo arms, respectively.
Following complete resection, 1943 patients (pT1b high grade to pT4 any grade disease, any node involvement) were classified based on risk (intermediate-high or very high), clear or non-clear histology, ECOG performance status, and surgery approach. Patients were then randomized 1:1:1 to receive 1 of the 2 TKIs or placebo for 1 year. Sorafenib was administered daily and sunitinib was administered daily for 4 weeks of a 6-week cycle.
The trial’s primary endpoint was DFS and was designed to find an improvement from 5.8 to 7.7 years (HR, 0.25). Secondary endpoints focused on overall survival (OS) and side effects of prolonged administration.
At an interim analysis, an independent data monitoring panel recommended release of the results, though no efficacy or futility boundaries were crossed. Patients in the sorafenib and sunitinib arms received a median of 8 cycles of therapy (range 1-9), while patients in the placebo arm received a median of 9 cycles (range 1-9).
OS rates were similar between all 3 arms. Five-year OS rates were 80.7% in the sorafenib arm (HR, 0.93; 97.5% CI, 0.69-1.23), 76.9% in the sunitinib arm (HR, 1.10; 97.5% CI, 0.83-1.45), and 78.7% in the placebo arm.
The most common grade ≥3 adverse events observed on the trial were hypertension (16%, 16%, 4%; for sorafenib, sunitinib, and placebo, respectively), hand-foot reaction (33%, 15%, 1%), rash (15%, 2%, 1%), and fatigue (7%, 17%, 3%).
Sunitinib is currently approved by the FDA for the treatment of advanced RCC, as well as pancreatic neuroendocrine tumors and gastrointestinal stromal tumors.
1. Haas NB, Manola J, Uzzo RG, et al. Initial results from ASSURE (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase III trial. 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL. Abstract 403.