2019 ASCO: No Benefit From Pazopanib in Advanced Renal Cell Carcinoma After Metastasectomy
The E2810 trial was conducted to determine whether treatment with the oral drug pazopanib following surgery to remove further metastases in patients with advanced renal cell carcinoma would improve their disease-free survival. Results from the study—which showed that primary endpoint of disease-free survival was not met—were presented by Appleman et al at the 2019 ASCO Annual Meeting (Abstract 4502).
“E2810 found that pazopanib treatment for 1 year did not improve the chance of survival without disease recurrence,” said lead trial investigator Leonard J. Appleman, MD, PhD, a medical oncologist at the University of Pittsburgh and the University of Pittsburgh Medical Center Hillman Cancer Center. “This finding is important because these patients are at particularly high risk of recurrence, and treatments shown to benefit patients with metastatic disease in place have been attractive to study after surgery to completely remove all visible sites of cancer.” These findings are consistent with earlier studies with other VEGF tyrosine kinase inhibitors.
Study Background
Following initial surgery, select patients with stage IV renal cell carcinoma may undergo metastasectomy to remove one or a very limited number of metastases that develop. This approach can remove all evidence of disease and can sometimes lead to durable control of disease—however, most patients ultimately recur. No systemic therapy has been shown to benefit this population, thus, the current standard of care outside of a clinical trial remains surveillance following the surgery to remove the metastases.
Pazopanib is an inhibitor of VEGFR and other kinases that is approved by the U.S. Food and Drug Administration for the treatment of metastatic renal cell carcinoma.
E2810 was a randomized, double-blind, placebo-controlled trial to test the hypothesis that pazopanib would improve disease-free survival in stage IV patients with no evidence of disease following metastasectomy.
From August 2012 to July 2017, 129 eligible patients were enrolled into the trial by physicians at 58 clinical sites across the U.S. Patients were randomly assigned 1:1 to receive pazopanib starting at 800 mg daily vs placebo for 52 weeks. Patients were stratified by 1 vs > 1 site of resected disease, and by disease-free interval ≤ vs > 1 year. Clinical assessments for toxicity and patient-reported outcomes were performed every 4 weeks and restaging scans were performed every 12 weeks.
Results
“The trial did not show a benefit and in fact, there was a suggestion that the patients who received pazopanib had a shorter lifespan,” said Dr. Appleman. “This observation was not statistically conclusive and longer follow up of the patients who participated in this study may clarify this observation.”
The median follow-up from randomization was 30 months (range 0.4–66.5 months). More than half the patients have had a recurrence of their cancer either during the treatment period or in later follow-up. Most (83%) of the patients are still alive and some have begun further treatment.
“Given the results of E2810, the role of adjuvant VEGF tyrosine kinase inhibitor therapy appears to be limited for both primary resected kidney cancer at high risk for recurrence and for resected metastases,” said co-investigator Naomi B. Haas, MD, a medical oncologist at the University of Pennsylvania and Co-Chair of the ECOG-ACRIN Genitourinary Cancer Research Committee. “This may be due to the absence of tumor blood vessels to target, compounded with an intolerable side effect profile in many patients. The focus has now turned to the role of immune checkpoint inhibition in both settings.”
Disclosure: The trial was designed and conducted by researchers in the ECOG-ACRIN Cancer Research Group with funding from the National Cancer Institute. For full disclosures of the study authors, visit coi.ascopubs.org.
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