Open-label phase II trial of everolimus monotherapy in treatment-naive patients with advanced papillary renal cell carcinoma.

Abstract

TPS234 Background: Papillary renal cell carcinoma (RCC) is genetically and morphologically distinct from other RCCs, and accounts for up to 10% of RCC diagnoses. All RCC histologies are generally resistant to chemotherapy. Newer targeted treatment approaches have demonstrated clinical benefit in patients with clear cell RCC, but options for the treatment of papillary RCC remain limited. Everolimus, an oral mTOR inhibitor, has demonstrated efficacy in the pivotal RECORD-1 study in patients with mRCC with a “clear cell component” histology that progressed on vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy, and everolimus is now indicated for use in this patient population. Because mTOR is also aberrantly activated in papillary RCC, mTOR inhibition presents a novel means for targeted therapy in papillary RCC. The ongoing RAPTOR (RAD001 in Advanced Papillary Tumor Program in Europe) trial is evaluating the efficacy and safety of everolimus monotherapy in treatment-naive patients with advanced papillary RCC. Methods: RAPTOR is an open-label, single-arm, non-randomized, single-stage, multicenter phase II trial currently recruiting participants. Up to 60 patients ≥18 years of age with a centrally confirmed histologic diagnosis of advanced type I or II metastatic papillary RCC, ≥1 measurable baseline lesion as per RECIST criteria, ECOG performance status of 0 or 1, and adequate liver, renal, and bone marrow function will be enrolled. Patients who have received prior systemic RCC therapy (ie, sorafenib, sunitinib, bevacizumab) are excluded. Patients will receive everolimus 10 mg/d orally until disease progression, unacceptable toxicity, death, or study discontinuation for any other reason. The primary study endpoint is PFS rate at 6 months. Disease control rate, objective response rate, duration of response, median PFS, overall survival, and safety will also be assessed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bayer Pharma, Pfizer, Roche Bayer, Genentech, Novartis, Pfizer, Roche