As reported in the Journal of Clinical Oncology by Leonard J. Appleman, MD, PhD, and colleagues, the phase II ECOG-ACRIN E2810 trial showed no significant improvement in disease-free survival with pazopanib vs placebo in patients with metastatic renal cell carcinoma with no evidence of disease after metastasectomy.
![Leonard J. Appleman, MD, PhD](/media/14020518/4-appleman.jpg)
Leonard J. Appleman, MD, PhD
Study Details
In the U.S. multicenter double-blind trial, 129 patients were randomly assigned between August 2012 and July 2017 to receive pazopanib at 800 mg (n = 66) or placebo (n = 63) once daily for 52 weeks. The study was designed to observe an improvement in 3-year disease-free survival from 25% to 45% with pazopanib, corresponding to a 42% reduction in the disease-free survival event rate.
Key Findings
Analysis at a median follow-up of 31.5 months showed an estimated 3-year disease-free survival rate of 25.4% (95% confidence interval [CI] = 15.4%–41.8%) in the pazopanib group vs 21.2% (95% CI = 12.0%–37.4%) in the placebo group, with the primary endpoint not being met. The hazard ratio (HR) for the pazopanib group vs the placebo group was 0.84 (95% CI = 0.54–1.29); median disease-free survival was 17 months vs 14.2 months.
Updated analysis at a median follow-up of 60.5 months showed a 3-year disease-free survival rate of 27.4% (95% CI = 17.9%–41.7%) in the pazopanib group vs 21.9% (95% CI = 13.3%–36.2%) in the placebo group (HR = 0.90, 95% CI = 0.60–1.34, P = .29). The study was not powered to assess overall survival; overall survival rate at 3 years was 81.9% (95% CI = 72.7%–92.2%) in the pazopanib group vs 91.4% (95% CI = 84.4%–98.9%) in the placebo group (HR = 2.55, 95% CI = 1.23–5.27).
Grade 3 or 4 adverse events more common in the pazopanib group included hypertension (35% vs 10%), diarrhea (16% vs 0%), and elevated alanine aminotransferase (14% vs 0%). Adverse events led to discontinuation of treatment in 24% vs 3% of patients. Health-related quality-of-life measures deteriorated in the pazopanib group during treatment.
The investigators concluded: “Pazopanib did not improve disease-free survival as the primary endpoint compared with blinded placebo in patients with metastatic renal cell carcinoma with no evidence of disease after metastasectomy. In addition, there was a concerning trend favoring placebo in overall survival.”
Dr. Appleman, of the UPMC Hillman Cancer Center, Pittsburgh, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.