Objective: Stomatitis is a common adverse event (AE) of mTOR inhibition. In BOLERO-2, all-grade (Gr), Gr–2 and 3 stomatitis incidence with EVE/EXE was 67%, 33%, and 8%, respectively. Median time to Gr –2 onset was 15.5 days; incidence plateaued at 6 weeks. In a meta- analysis of stomatitis among phase 3 trials, 89% of first stomatitis events occurred within 8 weeks. Topical steroids are used to treat aphthous ulcers; anecdotal use as prophylaxis has been reported. Prospective studies are ongoing to investigate prophylactic steroid-based rinses to prevent stomatitis. Nurses are critical in educating patients about and treatment of AEs. The SWISH trial evaluated prophylactic use of dexamethasone (DEX) MW in preventing stomatitis in PM women with HR+ MBC receiving EVE/EXE.
Methods: Eligible patients prescribed EVE 10 mg/EXE 25 mg QD received a commercially available alcohol-free DEX 0.5 mg/5 mL solution, 10 mL swished – 2 min and spit QID – 8 wks. Oral antifungal prophylaxis was optional. Patients completed a daily log for adherence, oral pain, and normalcy of diet scores. The primary end point compared the incidence of Gr –2 stomatitis at 8 weeks with BOLERO-2 results.
Results: Ninety-two patients enrolled; 86 were evaluable for efficacy. Median age was 61 years; >35% were treated with EVE/EXE in the –2nd-line setting. Twenty patients used antifungal prophylaxis. Incidence of Gr –2 stomatitis at 8 weeks was 2.4% versus 33% in BOLERO-2. Incidence of all-grade stomatitis at 8 weeks was 21.2% versus 67% in BOLERO-2. The rate of Gr 1 stomatitis was 18.8%. Median dose intensity was 10 mg and 25 mg for EVE and EXE, respectively. Ninety-five percent of patients used MW 3 to 4 times/day (median uses/day = 3.95). In the 75 patients with complete ECOG scores, 88% maintained/improved ECOG status. Mean pain scale score was <1 (very little pain) at all visits; 88% of patients reported normal diet at 8 weeks. Thirteen percent discontinued EVE/EXE due to suspected related AEs (most common: rash, hyperglycemia, and stomatitis [2% each] and pneumonitis [1%]). Oral candidiasis was reported in 2 patients; both patients used antifungal prophylaxis. Overall, DEX mouthwash was well tolerated with minimal toxicity.
Conclusions: Prophylactic use of 0.5 mg/5 mL DEX oral solution markedly decreased the incidence and severity of stomatitis in patients receiving EVE/EXE for MBC and should be considered a new standard of care in this setting. It is important to counsel patients on strategies to prevent stomatitis, such as DEX MW, prior to initiating EVE/EXE therapy.
Sponsorship: This study was sponsored by Novartis Pharmaceuticals Corporation (NCT02069093).
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