Final results of the international, expanded-access program of everolimus in patients with advanced renal cell carcinoma who progress after prior vascular endothelial growth factor receptor–tyrosine kinase inhibitor (VEGFr-TKI) therapy.

Abstract

4601 Background: The phase III RECORD-1 trial established everolimus as the only agent proven to benefit patients with metastatic renal cell carcinoma (mRCC) after failure of initial VEGFr-TKI therapy. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, more than doubled median progression-free survival compared with placebo, from 1.9 months to 4.9 months. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated in order to address an unmet medical need and provide everolimus in advance of regulatory approval and commercial availability to patients with mRCC after failure of initial VEGFr-TKI therapy. Methods: REACT was an open-label, international, expanded-access clinical trial (Clinicaltrials.gov: NCT00655252). Eligible patients had measurable or nonmeasurable mRCC of any histology, were intolerant of, or progressed while on, VEGFr-TKI therapy, had a Karnofsky performance score ≥70%, and had adequate bone marrow, hepatic, and renal function. Patients received everolimus 10 mg/day orally, with dose and schedule modifications allowed for toxicity. The primary objective of REACT was to evaluate the long-term safety of everolimus in patients with mRCC, as determined by the overall incidence of grade 3/4 and serious adverse events (AEs). Tumor response to everolimus was also assessed according to RECIST. Results: A total of 1367 patients from 34 countries were enrolled. Safety findings and tumor responses were consistent with those observed in RECORD-1. The most commonly reported grade 3/4 AEs were anemia (13.4%), fatigue (6.7%), and dyspnea (6.4%), and the most frequent serious AEs were dyspnea (5.0%), pneumonia (4.7%), and anemia (4.1%). Median dose intensity was 10.0 mg/day; relative dose intensity ranged from 0.90 to 1.10 in 68.9% of patients. Conclusions: REACT evaluated the safety and tolerability of everolimus in a broader patient population than the controlled trial RECORD-1. Everolimus was well tolerated, with no new safety issues identified and infrequent dose reductions/interruptions in the majority of patients.