Medical OncologySafety of Everolimus by Treatment Duration in Patients With Advanced Renal Cell Cancer in an Expanded Access Program
Section snippets
Study Design
The study design of REACT has been previously reported.9 Evaluation of everolimus safety in a large population of patients with mRCC who progressed on previous VEGFr-TKI therapy was the primary objective of REACT. Adult patients with mRCC who progressed on, or were intolerant of, previous VEGFr-TKI therapy were enrolled from 34 participating countries (Clinicaltrials.gov: NCT00655252). Enrollment commenced in July 2008 and was completed by June 2010. Protocol approval was sought and obtained
Patient Characteristics and Disposition
A total of 1367 patients from 34 countries enrolled in REACT were divided into 4 treatment duration strata: 626 to <3 months; 395 to ≥3 months and <6 months; 294 to ≥6 months and <1 year; and 52 to ≥1 year. Analysis of baseline characteristics (Table 1) revealed that a greater proportion of patients who received treatment for ≥6 months were aged <65 years compared with those who received treatment for <6 months. All patients who received everolimus for ≥1 year had tumors with clear cell
Discussion
Sequential administration of targeted therapies has now become the recommended standard of care for most patients with mRCC,2, 3, 4, 5 and patients will increasingly receive treatment with VEGFr-TKIs and mTOR inhibitors over longer time periods. Long-term administration of a targeted agent might lead to a high incidence of toxicities associated with treatment-related AEs. For example, in the phase 3 Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) trial of sorafenib,
Conclusions
Overall, everolimus is well tolerated in patients with mRCC for treatment durations of up to 1 year and longer. Certain mTOR inhibitor class-effect toxicities were more prevalent in patients receiving everolimus for >1 year, such as pneumonia, noninfectious pneumonitis, and hyperglycemia, but they do not appear to lead to treatment discontinuation. The first occurrence of AEs presented early in the course of treatment for most of the patients, suggesting that cumulative toxicity does not arise
Acknowledgments
The authors thank Tapas Chakraborty for analytical support.
References (18)
- et al.
mTOR inhibitors in advanced renal cell carcinoma
Hematol Oncol Clin North Am
(2011) - et al.
Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Ann Oncol
(2012) - et al.
EAU guidelines on renal cell carcinoma: the 2010 update
Eur Urol
(2010) - et al.
EORTC-GU group expert opinion on metastatic renal cell cancer
Eur J Cancer
(2009) - et al.
Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial
Lancet
(2008) - et al.
Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study
Eur J Cancer
(2012) - et al.
An international expanded-access programme of everolimus: Addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy
Eur J Cancer
(2012) - et al.
Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial
Lancet Oncol
(2009) - et al.
Long-term safety of sorafenib in advanced renal cell carcinoma: follow-up of patients from phase III TARGET
Eur J Cancer
(2010)
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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.