Everolimus in patients with metastatic renal cell carcinoma (mRCC) who are intolerant of or have progressed after prior vascular endothelial growth factor receptor–tyrosine kinase inhibitor (VEGFr-TKI) therapy: An international expanded access program (EAP).

Abstract

314 Background: The mammalian target of rapamycin (mTOR) inhibitor everolimus is the first agent to show efficacy in a randomized, controlled phase III trial in patients with mRCC after progression on VEGFr-TKIs (RECORD-1). Progression-free survival (PFS) was significantly improved (4.9 vs 1.9 months) and the risk of disease progression was reduced by 67% with everolimus compared with placebo. To fulfill an unmet medical need, everolimus was offered globally in this EAP. Presented here are preliminary results on 605 patients. Methods: The program began in July 2008 (ClinicalTrials.gov: NCT00655252 ; EudraCT: 2007-005460-28), and since then over 1,000 patients in 34 countries have been enrolled. Patients with clear cell and non–clear cell mRCC who failed or became intolerant of VEGFr-TKIs received daily oral doses of everolimus with investigator assessment every 3 months. Results: Data were collected for 605 patients who had discontinued treatment as of January 15, 2010. Evaluable patients had a mean age of 63 years, and most (94%) had progressed after prior VEGFr-TKI therapy. The adverse event (AE) profile did not differ significantly from that reported in the RECORD-1 trial. Most frequently reported grade 3–4 AEs were anemia (6.1%), stomatitis (4.6%), fatigue (4.6%), hyperglycemia (4.0%), and infection (3.6%). Grade 3–4 noninfectious pneumonitis was reported in 2.8%. Best overall response was stable disease, which was evident in 42% of patients. Conclusions: The EAP has allowed patients with mRCC access to everolimus before marketing approval. The rapid enrollment rate of this EAP confirms the unmet medical need after failure of VEGFr-TKIs. Everolimus has shown good tolerability, and no new safety issues have been identified. The investigator-assessed response rate is consistent with that reported in the RECORD-1 trial. The EAP provides an efficient framework for the development of other programs for innovative anticancer agents in patients without satisfactory therapeutic options. [Table: see text]