For E2810, patients with no evidence of disease following metastasectomy were randomized 1:1 to receive pazopanib starting at 800 mg daily versus placebo for 52 weeks. Patients were stratified by 1 vs > 1 site of resected disease, and by disease-free interval ≤ vs > 1 year. Key eligibility criteria included (i) synchronous or metachronous primary/metastases allowed, (ii) any number of resected metastases or past surgeries allowed, (iii) a clear cell histological component, (iv) no evidence of disease on baseline staging scans, (v) ECOG PS 0-1, (vi) enrolled within 12 weeks of surgery, and (vii) no prior systemic therapy. Clinical assessment for toxicity and patient-reported outcomes were performed every 4 weeks, and restaging scans every 12 weeks. The study was designed to observe a 42% improvement in disease-free survival (DFS) from 25% to 45% at 3 years. As follows is the study schema:
From August 2012 to July 2017, there were 129 patients enrolled: 66 patients in the pazopanib arm and 63 in the placebo arm. The study was unblinded after 83 DFS events had been observed (92% information). The median follow-up from randomization was 30 months (range 0.4 – 66.5 months). The study did not meet the primary endpoint as the hazard ratio for DFS was 0.85 (95% CI 0.55-1.31; p=0.47) in favor of pazopanib.
At the time of unblinding, 17% of subjects had died and the HR for OS was 2.65 (95% CI 1.02-6.9; p=0.05) in favor of placebo.
Dr. Appleman concluded his presentation of E2810 with the following points:
- Pazopanib did not improve DFS in patients with mRCC rendered surgically no evidence of disease by metastasectomy
- These results are consistent with PROTECT2 study of pazopanib after nephrectomy
- There was a trend toward decreased OS with pazopanib with early follow-up (16% event rate overall with median follow-up of 30 months)
- There remains an unmet need to investigate systemic therapy after metastasectomy for RCC – randomized studies are feasible, but sample size has limited statistical power
Presented by: Leonard J. Appleman, MD, PhD, UPMC Hillman Cancer Center, Pittsburgh, PA
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA
- Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 2013;369(8):722-731.
- Motzer RJ, Haas NB, Donskov F, et al. Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with locally advanced renal cell carcinoma (RCC) (PROTECT). J Clin Oncol 2017;35(35):3916-3923.