|The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
No improvement in disease-free survival (DFS) with adjuvant pazopanib was observed for patients with no evidence of disease (NED) following metastasectomy for renal cell carcinoma (RCC) when compared with placebo, according to results of a phase 3 trial presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
Although effective targeted therapy has become increasingly available for the systemic management of patients with metastatic RCC, the clinical benefit of this approach in patients with NED following metastasectomy was unknown at the start of the study.
In this randomized, placebo-controlled, double-blinded, phase 3 trial (ClinicalTrials.gov Identifier: NCT01575548), 129 patients with metastatic RCC and NED following metastasectomy were randomly assigned in a 1:1 ratio to receive pazopanib (800 mg once daily) — an antiangiogenic, multitargeted tyrosine kinase inhibitor that is also a standard of care for first-line systemic therapy in the setting of metastatic RCC — or placebo for 1 year.
The primary outcome measure of the study was DFS, with secondary end points including safety, overall survival (OS), patient-reported outcomes, and laboratory correlates.
“Patient-reported outcomes and laboratory correlates will be reported separately,” noted Leonard Appleman, MD, PhD, UPMC Hillman Cancer Center, Pittsburgh, Pennsylavia, who presented the study results related to safety and efficacy.
Patients were enrolled in the study within 4 weeks and 12 weeks of surgery, had a clear-cell component in the surgical specimen, and had not received prior systemic therapy for RCC. Patient baseline characteristics included an average age of 61 years, with metachronous disease present in the majority of patients.
At a median follow-up of 30 months from randomization, rates of 3-year DFS were 26% (pazopanib) and 22% (placebo) in the 2 study arms, with no significant change in DFS for patients receiving pazopanib compared with placebo (hazard ratio [HR], 0.85; 95% CI, 0.55-1.31) in favor of pazopanib.
“This was a negative study,” noted Dr Appleman.
Notably, the HR for OS was 2.65 (95% CI, 1.02-6.9) in favor of placebo (P =.05).
Regarding toxicity, no new safety signals were noted for patients receiving pazopanib. Rates of a number of adverse events, including fatigue, diarrhea, rash, and elevated transaminases were higher in the pazopanib arm compared with the placebo arm. A grade 5 adverse event involving intracranial hemorrhage occurred in 1 patient receiving pazopanib.
Dr Appleman concluded that these results are consistent with results of other recently reported studies in this setting, and that “there remains an unmet need to investigate systemic therapy after metastasectomy for RCC.”
Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.
Appleman LJ, Puligandla M, Pal SK, 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 following metastasectomy: A trial of the ECOG-ACRIN cancer research group (E2810). Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 4502.