SWISHing Steroid Mouthwash Combats Everolimus-Related Stomatitis

Everolimus-induced stomatitis is preventable by regular rinsing with a dexamethasone mouthwash

medwireNews: Prophylactic dexamethasone mouthwash significantly reduces the risk of developing grade 2 and more severe everolimus -related stomatitis, suggests the SWISH study of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer.

“Steroid prophylaxis should be considered a new standard of oral care for postmenopausal patients who are receiving everolimus and exemestane for treatment of hormone receptor-positive, HER2-negative advanced breast cancer and metastatic breast cancer, especially in the first 8 weeks of treatment and as needed thereafter”, the authors recommend in The Lancet Oncology.

“In the future, steroid prophylaxis might be considered as a treatment option in other diseases for which everolimus is indicated (advanced renal cell carcinoma, subependymal giant cell astrocytoma associated with tuberous sclerosis complex, and advanced neuroendocrine tumours)”, they believe.

The phase II trial included 92 women who were asked to swish with 10 mL of alcohol-free dexamethasone 0.5 mg/5 mL solution for up to 2 minutes four times a day for 8 weeks, beginning from day 1 of their first cycle of everolimus 10 mg/day plus exemestane 25 mg/day.

Grade 2 or worse stomatitis occurred in 2% of the 85 assessed patients over 8 weeks compared with 33% of 482 participants of the BOLERO-2 study who used everolimus plus exemestane without mouthwash and served as historical controls.

The difference in stomatitis incidence was significant between the two groups despite the BOLERO-2 patients having a lower median dose intensity of everolimus at 8 weeks than their SWISH counterparts, at 8.6 versus 10.0 mg, report Hope Rugo, from the University of California San Francisco in the USA, and co-authors.

“The favourable dose intensity for everolimus and exemestane that was recorded in this trial might be a consequence of the reduced incidence of stomatitis, as well as the fact that dexamethasone mouthwash treatment was well tolerated with minimal toxicity”, they suggest.

The incidence of all-cause, all-grade stomatitis was also lower at week 8 with mouthwash use, at 21% versus 61% in controls.

The most common grade 3 adverse events related to treatment in the 92 patients with safety assessment were hyperglycaemia (5%), rash (3%) and pneumonitis (2%) or pneumonia (2%), while dyspnoea was the most common grade 4 event, affecting 2%.

Patient-reported outcomes at week 8 were also assessed in 72 patients, at which time 94% were able to maintain a diet with no or few restrictions and the average oral pain score was below 1 at all visits. The majority (90%) of patients were able to brush their teeth once or twice daily and 88% improved or maintained their ECOG performance status.

The authors of a linked comment say the SWISH investigators “should be commended for a well-conducted study of a cost-effective measure to prevent a potentially debilitating side-effect.”

Noting that 95% of 86 patients reported using the mouthwash three or four times a day, they suggest that the high rate of mouthwash adherence may be linked to oral hygiene education during the trial and not reflect “real-world” use, but add that the prodrome associated with everolimus-related oral mucositis might allow treatment to begin at first sign rather than as a preventative regimen.

Laura Spring and Aditya Bardia, from Harvard Medical School in Boston, Massachusetts, USA, also observe that current patients with hormone receptor-positive, HER2-negative metastatic breast cancer are likely to receive CDK 4/6 inhibitor plus endocrine therapy before everolimus plus exemestane.

Nevertheless, the commentators conclude: “Many patients with hormone receptor-positive metastatic breast cancer, particularly those with osseous metastases only, have a life expectancy measured in years and the goals for systemic treatment are to prolong survival while maintaining quality of life.

“Accordingly, in the era of targeted therapies and precision medicine, studies such as the SWISH trial, dedicated to the mitigation of adverse effects from targeted therapies to improve quality of life and tolerability, are particularly refreshing.”


Rugo HS, Seneviratne L, Thaddeus Beck J, et al. 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. Lancet Oncol; Advance online publication 14 March 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30109-2

Spring L, Bardia A. SWISH-ing steroids: new standard of care to prevent everolimus-induced oral mucositis. Lancet Oncol; Advance online publication 14 March 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30106-7

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