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Medline ® Abstract for Reference 17

of 'Oral toxicity associated with chemotherapy'

17
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Meta-analysis of stomatitis in clinical studies of everolimus: incidence and relationship with efficacy.
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Rugo HS, Hortobagyi GN, Yao J, Pavel M, Ravaud A, Franz D, Ringeisen F, Gallo J, Rouyrre N, Anak O, Motzer R
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Ann Oncol. 2016;27(3):519. Epub 2016 Jan 11.
 
BACKGROUND: Everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, is used to treat solid tumors and tuberous sclerosis complex (TSC). Stomatitis, an inflammation of the mucous membranes of the mouth, is a common adverse event associated with mTOR inhibitors, including everolimus. We conducted a meta-analysis of data from seven randomized, double-blind phase 3 clinical trials of everolimus to determine the clinical impact of stomatitis on efficacy and safety.
PATIENTS AND METHODS: Data were pooled from the safety sets of solid tumor [breast cancer (BOLERO-2 and BOLERO-3), renal cell carcinoma (RECORD-1), carcinoid tumors (RADIANT-2), and pancreatic neuroendocrine tumors (RADIANT-3)]and TSC studies (EXIST-1 and EXIST-2). Data from solid tumor trials and TSC trials were analyzed separately.
RESULTS: The rate of stomatitis was 67% in the solid tumor trials (973/1455 patients) and 70% in the TSC trials (110/157 patients). Most stomatitis events were grade 1/2, with grade 3/4 events reported in only 9% (solid tumor trials) and 8% (TSC trials) of patients. Low TSC patient numbers prevented an in-depth evaluation of stomatitis and response. In the solid tumor trials, most first stomatitis episodes (89%; n = 870) were observed within 8 weeks of starting everolimus. Patients with stomatitis occurring within 8 weeks of everolimus initiation had longer progression-free survival (PFS) than everolimus-treated patients without stomatitis in BOLERO-2 {8.5 versus 6.9 months, respectively; hazard ratio (HR), 0.78 [95% confidence interval (CI), 0.62-1.00]} and RADIANT-3 [13.9 versus 8.3 months, respectively; HR, 0.70 (95% CI, 0.48-1.04)]. A similar trend was observed in RECORD-1 [HR, 0.90 (95% CI, 0.66-1.22)]and RADIANT-2 [HR, 0.87 (95% CI, 0.61-1.22)]but not in BOLERO-3 [HR, 1.01 (95% CI, 0.75-1.36)].
CONCLUSIONS: Stomatitis did not adversely affect PFS, supporting the administration of everolimus in accordance with standard management guidelines.
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University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco hope.rugo@ucsf.edu.
PMID