Sunitinib improved overall survival in metastatic RCC

Sunitinib was safe, effective first-line treatment compared with IFN-alpha.

In a final survival analysis of a phase-3 trial, first-line treatment with sunitinib resulted in greater OS than interferon alpha in patients with metastatic renal cell carcinoma.

The findings of this trial confirm that sunitinib is an appropriate reference standard for future phase-3 clinical trials, according to Walter M. Stadler, MD, professor of medicine at the University of Chicago Medical Center.

“Perhaps most importantly, sunitinib is representative of the vascular endothelial growth factor pathway inhibitor class of agents that, along with the mammalian target of rapamycin inhibitors, have revolutionized the treatment of renal cancer patients,” he said in an accompanying editorial.

In the trial, 750 patients with metastatic renal cell carcinoma from 101 international centers were randomly assigned to sunitinib (Sutent, Pfizer) 50 mg once daily, four weeks on, two weeks off, or subcutaneous interferon alpha (Roferon-A, Roche) three times a week.

The median duration of treatment was 11 months for sunitinib and four months for interferon alpha.

Overall survival improved

By unstratified log-rank test, median OS was 26.4 months with sunitinib vs. 21.8 months with interferon alpha (HR=0.821; 95% CI, 0.673-1.001).

Sunitinib also resulted in a higher response rate than interferon alpha (47% vs. 12%; P<.001) and a higher median PFS (11 months vs. five months; P<.001).

The researchers analyzed the benefit of sunitinib compared with interferon alpha controlling for prognostic risk factors and found that the treatment effect of sunitinib was statistically significant (HR=0.764; 95% CI, 0.623-0.936).

Using the Memorial Sloan-Kettering Cancer Center criteria, researchers categorized patients into favorable-, intermediate- and poor-risk groups. OS was higher for patients assigned sunitinib in the intermediate-risk group (20.7 months vs. 15.4 months) and the poor-risk group (5.3 months vs. 4.0 months) compared with the interferon alpha group. Median OS was not reached in the favorable-risk group.

Cross over treatment

In exploratory analysis of 25 patients assigned interferon-alpha who crossed over to sunitinib, the median OS time was 26.4 months in the sunitinib group and 20.0 months in the interferon alpha group (HR=0.808; 95% CI, 0.661-0.987).

In the subset of patients who were not assigned to any poststudy cancer treatment, the median overall survival rate was 28.1 months in the sunitinib group vs. 14.1 months in the interferon alpha group (HR=0.647; 95% CI, 0.483-0.870).

With sunitinib treatment, the most commonly reported grade-3 adverse events were hypertension, fatigue, diarrhea and hand-foot syndrome.

Motzer RJ. J Clin Oncol. 2009;doi:10.1200/JCO.2008.20.1293.