International, expanded access program of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy (VEGFr-TKI): Subanalysis from emerging growth market (EGM) countries.
e15047 Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor shown to benefit patients with mRCC after failure of initial VEGFr-TKI therapy. In the phase 3 RECORD-1 trial, median progression-free survival was 4.9 months with everolimus and 1.9 months with placebo (hazard ratio, 0.33; P < .001). REACT (RAD001 Expanded Access Clinical Trial in RCC; NCT00655252) was an open-label, expanded access program that provided everolimus before commercial availability to 1367 patients with VEGFr-TKI refractory mRCC in 34 countries. Final results of REACT were recently published (Eur J Cancer. 2012;48:324-332). Methods: The primary objective of REACT was to evaluate the long-term safety of everolimus 10 mg/day as determined by the overall incidence of grades 3 and 4 adverse events (AEs). Best overall tumor response was assessed according to RECIST 1.0. This subanalysis was conducted to assess primary and secondary end points in a subgroup of patients from 11 EGM countries: Turkey, Australia, Russia, Israel, Lebanon, Jordan, Saudi Arabia, South Korea, Singapore, Taiwan, and Thailand. Results: Baseline characteristics of the EGM population (n = 243) were similar to the overall REACT population: median age, 60.0 years; clear cell histology, 95.1%; and progression on/intolerance to previous VEGFr-TKI therapy, 89.7%/16.9%. Median duration (range) of everolimus exposure was 20.4 (0.3-83.7) weeks. Clinical benefit was observed in 60.1%/53.3% of EGM patients/all patients (stable disease, 55.6%/51.6%; partial response, 4.5%/1.7%). Common grade ≥3 AEs in EGM patients/all patients included anemia (19.8%/13.4%), pneumonia (7.4%/4.2%), hyperglycemia (7.0%/5.5%), stomatitis (5.8%/5.4%), and pneumonitis (2.9%/2.7%); 13.2%/16.6% of EGM patients/all patients discontinued because of AEs. Conclusions: In patients from EGM countries, safety findings and tumor responses were consistent with the overall REACT population and with RECORD-1. Everolimus was well tolerated, with no new safety issues identified.