Dexamethasone Mouthwash in Preventing Everolimus-Related Stomatitis in Women With Breast Cancer
In the phase II SWISH study reported in The Lancet Oncology, Rugo et al found that use of a dexamethasone-based mouthwash may prevent everolimus-related stomatitis in postmenopausal women receiving everolimus (Afinitor) for hormone receptor–positive, HER2-negative metastatic breast cancer. Stomatitis is a class effect of mTOR inhibitor treatment.
Study Details
The study included 92 women (85 evaluable) enrolled between May 2014 and October 2015 at 23 U.S. sites. Patients started treatment with everolimus at 10 mg plus exemestane at 25 mg daily and with mouthwash consisting of 10 mL of alcohol-free dexamethasone at 0.5 mg/5 mL oral solution. Patients swished the mouthwash for 2 minutes and then spit, 4 times daily, starting on the first day of treatment, for 8 weeks. After 8 weeks, use of the mouthwash could be continued for up to 8 additional weeks at clinician and patient discretion.
The primary endpoint was the incidence of grade ≥ 2 stomatitis by 8 weeks in patients who received at least one dose of everolimus and exemestane and at least one confirmed dose of dexamethasone mouthwash (evaluable patients), as compared with 482 historical controls from the BOLERO-2 trial; in BOLERO-2, patients received everolimus and exemestane for hormone receptor–positive advanced breast cancer and were not given dexamethasone mouthwash.
Incidence of Stomatitis
By 8 weeks, grade ≥ 2 stomatitis had occurred in 2 (2%, all grade 2) of 85 patients (95% confidence interval [CI] = 0.29%–8.24%), compared with 159 (33%) of 482 control patients (95% CI = 28.8%–37.4%) for the duration of the BOLERO-2 study. By 8 weeks, grade ≥ 2 stomatitis had occurred in 132 patients (27%) in the BOLERO-2 population. Grade 2 stomatitis resolved to grade 1 or lower after 11 days and 15 days in the 2 SWISH patients, respectively. The incidence of any-grade stomatitis was 21% in the SWISH patients by 8 weeks, compared with 67% in the BOLERO-2 patients within 13 months.
A total of 64 SWISH patients continued all treatment beyond 8 weeks. Six had a first episode of grade 1 or 2 stomatitis after week 8 (between 64 days and 98 days), and four were considered related to everolimus and exemestane treatment. All 6 patients had continued mouthwash beyond 8 weeks (time on treatment from 63 and 115 days). One case of grade 3 stomatitis occurred at day 95 and led to discontinuation of everolimus and exemestane in a patient who previously had 4 grade 1 events during the initial 8-week period.
Adverse Events
Nystatin antifungal prophylaxis was used by 4 of the 18 patients who developed grade 1 or 2 stomatitis by 8 weeks and by 20 patients overall. Two patients developed oral candidiasis during antifungal prophylaxis, which resolved with nystatin or oral fluconazole treatment.
Among all 92 patients, the most common grade 3 or 4 adverse events were hyperglycemia (8%), rash (4%), and dyspnea (3%). Serious adverse events occurred in 22%. Adverse events suspected considered possibly related to treatment led to discontinuation of everolimus and exemestane in 13%, including rash, hyperglycemia, and stomatitis in 2% each.
The investigators concluded: “Prophylactic use of dexamethasone oral solution substantially reduced the incidence and severity of stomatitis in patients receiving everolimus and exemestane and could be a new standard of oral care for patients receiving everolimus and exemestane therapy.”
The study was funded by Novartis Pharmaceuticals Corporation.
Hope S. Rugo, MD, of the University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
