We want treatments that help patients obtain disease control for longer and will maintain or improve their quality of life. The dexamethasone mouthwash meets that need.— Hope S. Rugo, MD
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Dexamethasone mouth rinse should be given prophylactically to prevent stomatitis associated with everolimus (Afinitor)/exemestane in metastatic breast cancer, according to Hope S. Rugo, MD, principal investigator of the SWISH trial and Director of Breast Oncology and Clinical Trials Education at the University of California Helen Diller Family Comprehensive Cancer Center, San Francisco. “This should be considered a new standard of oral care in this setting,” Dr. Rugo said at the 2016 Palliative Care in Oncology Symposium.
The SWISH trial sought to evaluate an alcohol-free, steroid mouthwash to prevent grade ≥ 2 stomatitis in patients with HER2-positive advanced breast cancer receiving everolimus/exemestane.1 The comparator was historical data from the BOLERO-2 trial.2
At the 2016 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology International Symposium on Supportive Care in Cancer in Adelaide, Australia, Dr. Rugo presented the main results of the SWISH trial, with outcomes spanning the duration of the study.3 (For more on this presentation, see the August 10 issue of The ASCO Post.) At the Palliative Care in Oncology Symposium, she focused on the 8-week outcomes; by 8 weeks, 89% of BOLERO-2 patients with stomatitis had experienced a first event.
Stomatitis is a frequent adverse event associated with mTOR (mammalian target of rapamycin) inhibition, observed in 67% of patients in the BOLERO-2 trial. A total of 33% were grade ≥ 2, and 8% were grade 3.
The basis for evaluating the dexamethasone mouthwash is the efficacy observed for topical steroids in idiopathic aphthous ulcers (ie, small shallow lesions on mucous membranes). These ulcers often respond to steroid dental paste (topical triamcinolone). In fact, Dr. Rugo has been using the dental paste to treat the stomatitis that sometimes occurs with other drugs, such as palbociclib (Ibrance), she said. “Because mTOR stomatitis looks like aphthous ulcers, we sought to explore whether a steroid-based mouthwash would prevent this toxicity,” she explained.
Key Findings and Clinical Implications
In the open-label phase II SWISH trial, 92 patients were instructed to use the mouthwash (10 mL containing 0.5 mg/5 mL of dexamethasone) to swish for 2 minutes, then spit, four times a day for 8 weeks. At the completion of cycle 2 (day 56), patients could continue the mouthwash regimen for an additional 56 days, if desired. In the study, 95% of patients used the mouthwash as instructed, and 70% continued it for 8 weeks or longer.
In patients who used the mouthwash, the incidence of grade ≥ 2 stomatitis by 8 weeks was 2.4%, compared with 27.4% in the BOLERO-2 trial and 33% over the entire BOLERO-2 study duration (P < .001).2 No patients using the mouthwash developed grade 3 or 4 stomatitis, whereas in BOLERO-2, grade 3 stomatitis occurred in 7.3%. No stomatitis occurred in 78.8% of the SWISH population, compared with 38.8% of the BOLERO-2 patients, Dr. Rugo reported.
Dexamethasone Mouth Rinse for Stomatitis
- The SWISH trial showed that daily use of dexamethasone mouth rinse was well tolerated and significantly lowered the incidence of stomatitis in postmenopausal women receiving everolimus and exemestane for metastatic breast cancer.
- At 8 weeks, the incidence of grade ≥ 2 stomatitis was 2.4%, compared with 27.4% in the BOLERO-2 population (P < .001), the historical control group.
- For occasional patients who develop stomatitis beyond 8 weeks, they can start and stop the mouthwash as needed, depending on the appearance of mouth sores.
- The mouthwash, which is simply the liquid pediatric formulation of dexamethasone, could be a new standard of care for stomatitis in this and perhaps other patient populations.
Of the 25 patients (27.2%) who did develop some degree of stomatitis in the SWISH study, 6 experienced their first episode after 8 weeks (days 65–98), all of which were grade 1 or 2. Half of these patients had discontinued dexamethasone prior to the documentation of stomatitis.
“We were interested to see who developed stomatitis after 8 weeks, and we found events in six patients. They were still on everolimus, and half had stopped the dexamethasone before they developed stomatitis. They were allowed to continue the mouthwash at whim,” revealed Dr. Rugo.
“This suggests that if you are at risk and continue the mouthwash on and off, you have less stomatitis. If you stop it and develop mouth sores, you can restart it,” explained Dr. Rugo. “A reasonable approach would be for the patient to titer the mouthwash to what seems to prevent the stomatitis. Basically, patients can swish a few times a day, and if they stop and don’t get sores, then fine. If they get a sore, they can start again.”
Dr. Rugo emphasized the need to minimize the occurrence of stomatitis in patients receiving the everolimus regimen. “A lot of patients in BOLERO-2 didn’t tolerate treatment because of stomatitis. When the combination was approved, the worldwide response was, ‘Patients get mouth sores,’” she said in an interview. “So if we can do something so simple to markedly reduce this common and potentially serious toxicity, we should. We want treatments that help patients obtain disease control for longer and will maintain or improve their quality of life. The dexamethasone mouthwash meets helps to meet that need.”
The mouthwash is simply a liquid formulation of dexamethasone and is easy for physicians to prescribe in the United States, she added. In countries where there are no liquid formulations, a compounded preparation could be prepared. ■
Disclosure: Dr. Rugo has received honoraria and is on the speakers bureau of Genomic Health; has received institutional funding from Celsion, Eisai, Genentech, GlaxoSmithKline, Lilly, MacroGenics, Merck, Nektar, Novartis, OBI Pharma, Pfizer, and Plexxikon; and has received travel expenses from Mylan, Novartis, Pfizer, OBI Pharma, Syndax, and Roche/Genentech.
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