Pazopanib Failed to Improve Long-Term Survival Results Among Patients With Metastatic Renal Cell Carcinoma Post-Metastasectomy at High Risk of Recurrence

According to results from the ECOG-ACRIN E2810 study, pazopanib, a VEGF receptor tyrosine kinase inhibitor, did not improve long-term disease-free survival (DFS) or overall survival (OS) among patients with metastatic renal cell carcinoma who had no evidence of disease after metastasectomy at high risk of recurrence. 

“Long-term survival is uncommon in patients with metastatic renal cell carcinoma even with contemporary doublet systemic therapy,” stated Leonard J. Appleman, MD, PhD, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, and coauthors. “The high risk of recurrence after metastasectomy demonstrates an unmet need for effective systemic therapy in the no evidence of disease setting.”

In this double-blind, placebo-controlled study, 129 patients with metastatic renal cell carcinoma with no evidence of disease after metastasectomy, at high risk of recurrence were randomized on a 1-to-1 basis to receive either 800 mg of once daily pazopanib (n = 66) or placebo (n = 63) for 52 weeks. The primary end point was DFS. Secondary end points included 3-year DFS, OS, and safety.

After 83 DFS events occurred, the study was unblinded and the primary end point was not met. At a follow-up of 60.5 months, 3-year DFS was 25.4% in the pazopanib arm and 21.2% in the placebo arm (hazard ratio [HR] 0.90; 95% confidence interval [CI], 0.60 to 1.33; one sided P = .29). OS was 81.9% in the pazopanib arm and 91.4% in the placebo arm (HR 2.55; 95% CI, 1.23 to 5.27; two-sided P = .012). Grade ≥3 treatment-related adverse events were experienced by 36% of patients in the pazopanib arm and 5% of patients in the placebo arm. Among patients treated with pazopanib, the most frequent treatment-related adverse events of any grade included diarrhea, elevated alanine aminotransferase, and hypertension. 

Dr Appleman et al concluded that this study found “pazopanib did not improve DFS after metastasectomy compared with placebo and does not support the use of pazopanib in patients with [metastatic renal cell carcinoma] surgically rendered [no evidence of disease].”

“The ASCO guidelines for management of clear cell RCC with low volume metastatic disease remains metastasectomy or other local therapy,” stated Journal of Clinical Oncology associate editor Gary K. Schwartz, MD, Columbia University Medical Center, New York, New York.

Source: 

Appleman LJ, Kim SE, Harris WB, et al. Randomized, double-blind phase III study of pazopanib versus placebo in patients with metastatic renal cell carcinoma who have no evidence of disease after metastasectomy: ECOG-ACRIN E2810. J Clin Oncol. Published online: March 26, 2024. doi:10.1200/JCO.23.01544