Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial
- Study type
- Clinical trial
- Study name
- SWISH
- Phase
- Phase 2
- Design
- Multicentre, single-arm, phase 2 prevention trial in the United States, compared with historical controls from the BOLERO-2 trial
- Sample size
- 92 patients enrolled; 85 patients evaluable for efficacy
- Source
- The Lancet Oncology · 2017
- Trial registration
- NCT02069093
In plain words
The drug everolimus, used in metastatic breast cancer, often causes painful sores and inflammation in the mouth (stomatitis). In this study, women used a mouthwash containing dexamethasone (a steroid) from the very start of treatment. Only about 2% of them developed moderate or worse stomatitis by week eight, compared with about 33% in an earlier study without the mouthwash. This mouthwash can help reduce mouth problems, but it should be used on your treating doctor's advice.
Key results
Treatment arms and regimens
Everolimus: 10 mg orally once daily, from day 1 of cycle 1.
Exemestane: 25 mg orally once daily.
Dexamethasone mouthwash: 10 mL of alcohol-free dexamethasone oral solution 0.5 mg per 5 mL (that is, 1 mg per use), swished in the mouth for 2 minutes and then spat out (not swallowed), four times daily for 8 weeks; nothing to be eaten or drunk for one hour after each use (per ClinicalTrials.gov). After 8 weeks, continuation for up to another 8 weeks at the discretion of physician and patient.
Source of the regimen details: Abstract of the paper and ClinicalTrials.gov NCT02069093
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Women over 18 years, postmenopausal (age 55 years or older with one year of amenorrhoea; under 55 years with one year of amenorrhoea and oestradiol below 20 pg/mL; or bilateral oophorectomy — ovarian suppression by radiation or an LHRH agonist was not allowed), with histologically or cytologically confirmed hormone receptor-positive, HER2-negative metastatic or locally advanced breast cancer not amenable to curative treatment, whose treating physician intended to start everolimus 10 mg + exemestane 25 mg daily; ECOG 0 to 2; serum creatinine ≤1.5 times the upper limit of normal; no stomatitis/mouth ulcers at baseline (oral pain of zero on a VAS).
Main exclusion criteria: concurrent anticancer therapy (except bisphosphonates and denosumab), uncontrolled diabetes (HbA1c above 8%), chronic systemic corticosteroids or immunosuppressants, severe impairment of lung function and a live vaccine within one week before starting everolimus (per ClinicalTrials.gov).
Endpoints
Primary endpoint: incidence of grade 2 or worse stomatitis by week 8 in the full analysis set (at least one dose of everolimus and exemestane and at least one confirmed dose of mouthwash), compared with historical controls from BOLERO-2 (everolimus + exemestane without dexamethasone mouthwash). Secondary endpoints (ClinicalTrials.gov): stomatitis of any grade, time to resolution of stomatitis, number of mouthwashes per day, dose intensity of everolimus and exemestane, and their blood concentrations.
Safety and side effects
The most common grade 3 and 4 adverse events in the safety set: hyperglycaemia (7 of 92 patients; 8%), rash (4 patients; 4%) and dyspnoea (3 patients; 3%). Serious adverse events were reported in 20 patients (22%); 6 (7%) were considered treatment-related, most commonly dyspnoea (3 patients; 3%) and pneumonia (2 patients; 2%). In 12 patients (13%), adverse events suspected to be treatment-related led to discontinuation of everolimus and exemestane (most common: rash, hyperglycaemia and stomatitis, 2 patients [2%] each). Overall, 83 patients (90%) had at least one adverse event.
Clinical significance and place in guidelines
According to the abstract, prophylactic dexamethasone mouthwash substantially reduced the incidence and severity of stomatitis in patients treated with everolimus and exemestane, and the authors considered that it could be a new standard of oral care. Because the study was single-arm with comparison against historical controls, its status in clinical guidelines and regulatory approvals should be checked separately.
Limitations
The study was single-arm with no concurrent randomised control group; the comparison with historical controls from the BOLERO-2 trial may be prone to bias. Of 92 patients enrolled, 85 were evaluable for efficacy. The study was funded by Novartis.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.