Objective: To retrospectively analyze the effects of treatment duration on outcomes of everolimus treatment of patients in the RAD001 Expanded-Access Clinical Trial in RCC (REACT) program. Methods: Patients with metastatic renal cell carcinoma refractory to vascular endothelial growth factor receptor-tyrosine kinase inhibitor received everolimus (10 mg once daily), with dosing interruption or modifications allowed for toxicity. All serious and grade 3/4 adverse events and grade 1/2 adverse events leading to a change in drug administration were reported. Tumor response was evaluated using Response Evaluation Criteria In Solid Tumors. Results: The study stratified 1367 evaluable patients into treatment duration groups of <3 months, ≥3 and <6 months, ≥6 months and <1 year, and ≥1 year. Pneumonia, noninfectious pneumonitis, and hyperglycemia occurred more frequently in patients receiving everolimus for ≥1 year but did not result in treatment discontinuations. First occurrence of adverse events presented early in the treatment course for most patients. Treatment duration of ≥6 months was associated with improved disease control rates. Conclusion: Everolimus is well tolerated in patients with metastatic renal cell carcinoma for treatment durations ≥1 year and not associated with cumulative toxicity.
Bibliographical noteFunding Information:
Financial Disclosure: S. Bavbek has received consulting fees and honoraria from Novartis, Pfizer, GlaxoSmithKline, Sanofi-Aventis, and Bayer. S. Bracarda has received consulting fees from Pfizer, Sanofi-Aventis, Jannsen, Boehringer-Ingelheim, GlaxoSmithKline, and Novartis and has held nonremunerative positions of influence for Bayer Schering Pharma. A. Bahl has received research grants from Sanofi and served as advisor to Sanofi, Amgen, Roche, and Novartis. D. Kim and O. Anak own stock in and are employees of Novartis. A. Panneerselvam is an employee of Novartis. V. Grünwald has received consulting fees and served as speaker for Pfizer. Other authors have no disclosures.
Funding Support: Editorial assistance in the preparation of this manuscript was provided by Karen Miller-Moslin, Ph.D., and Clare Lee, Ph.D., of ApotheCom (Yardley, PA), and was funded by Novartis Pharmaceuticals Corporation .
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