Sutent Extends Disease-Free Survival in Kidney Cancer

When used as an adjuvant therapy for patients with renal cell carcinoma (RCC) at high risk of recurrence, Sutent (sunitinib) extended disease-free survival (DFS) when compared with placebo in the phase 3 S-TRAC trial, according to Pfizer, the manufacturer of the multitargeted tyrosine kinase inhibitor (TKI).

The safety profile for Sutent 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 European Society of Medical Oncology (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, 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 3 S-TRAC trial randomized more than 670 patients at high-risk of RCC recurrence to adjuvant Sutent 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 3 ASSURE trial had not shown a positive outlook for Sutent in the adjuvant RCC setting. In the study, neither Sutent nor Nexavar (sorafenib) improved outcomes when administered after surgery to patients with locally advanced RCC.

The median DFS was 5.6 years in both the Nexavar and Sutent arms and 5.7 years in the placebo arm. The five-year DFS rate was 52.8 percent in the Nexavar arm, 53.8 percent in the Sutent arm, and 55.8 percent in the placebo arm. In total, there were 272, 265 and 270 DFS events observed in the Nexavar, Sutent, and placebo arms, respectively.

Following complete resection, 1,943 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 ratio to receive one of the two TKIs or placebo for one year. Nexavar was administered daily and Sutent was administered daily for four weeks of a six-week cycle.

The trial’s primary endpoint was DFS and was designed to find an improvement from 5.8 to 7.7 years. 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 Nexavar and Sutent arms received a median of eight cycles of therapy (range one to nine), while patients in the placebo arm received a median of nine cycles (range one to nine).

OS rates were similar between all three arms. Five-year OS rates were 80.7 percent in the Nexavar arm, 76.9 percent in the Sutent arm, and 78.7 percent in the placebo arm.

The most common grade 3 or higher adverse events observed on the trial were hypertension (16 percent, 16 percent, 4 percent; for Nexavar, Sutent, and placebo, respectively), hand-foot reaction (33 percent, 15 percent, 1 percent), rash (15 percent, 2 percent, 1 percent) and fatigue (7 percent, 17 percent, 3 percent).

Sutent is currently approved by the FDA for the treatment of advanced RCC, as well as pancreatic neuroendocrine tumors and gastrointestinal stromal tumors.