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
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.
