Adjuvant treatment with the monoclonal antibody girentuximab provided no clinical benefit to patients with high-risk clear cell renal cell carcinoma (ccRCC), according to a study published in JAMA Oncology.1
Girentuximab is a monoclonal antibody that binds carbonic anhydrase IX, a cell surface glycoprotein expressed in ccRCC. Because phase 2 studies demonstrated that girentuximab possesses activity with a manageable safety profile in ccRCC, researchers sought to evaluate its efficacy and safety as adjuvant monotherapy in a phase 3 trial.
For the international, double-blind, ARISER trial (Adjuvant Rencarex Immunotherapy Phase 3 Trial to Study Efficacy in Nonmetastatic RCC; ClinicalTrials.gov Identifier: NCT00087022), researchers enrolled 864 patients who had undergone partial or radical nephrectomy for histologically confirmed ccRCC. Patients were included if they had pT3/pT4Nx/N0M0, pTanyN+M0 or pT1b/pT2Nx/N0M0 disease with nuclear grade 3 or greater.
Participants were randomly assigned 1:1 to receive girentuximab intravenously weekly for 24 weeks or placebo. Co-primary end points were disease-free survival and overall survival.
Results showed that there was no significant difference in disease-free survival (hazard ratio [HR], 0.97; 95% CI, 0.79-1.18) or overall survival (HR, 0.99; 95% CI, 0.74-1.32) between patients treated with girentuximab and those who received placebo.
Median disease-free survival was 71.4 months with girentuximab and not reached in the placebo arm. Median overall survival was not reached in either treatment arm.
Four percent of patients in each arm reported serious adverse events, with only 1 treatment-related serious adverse event occurring in the placebo arm. There were no treatment-related deaths due to an adverse event.
Despite the excellent tolerability of girentuximab, the findings ultimately suggest that girentuximab is not beneficial for patients with resected localized RCC at high risk of recurrence.
1. Chamie K, Donin NM, Klopfer P, et al. Adjuvant weekly girentuximab following nephrectomy for high-risk renal cell carcinoma. JAMA Oncology. 2016 Oct 27. doi: 10.1001/jamaoncol.2016.4419. [Epub ahead of print]