Prevention of everolimus/exemestane (EVE/EXE) stomatitis in postmenopausal (PM) women with hormone receptor-positive (HR+) metastatic breast cancer (MBC) using a dexamethasone-based mouthwash (MW): Results of the SWISH trial.

Abstract

525 Background: Stomatitis is a significant complication associated with mTOR inhibition. In BOLERO-2 patients (pts) receiving EVE/EXE, all grade (Gr) stomatitis was 67%; 33% had Gr ≥ 2 and 8% Gr 3. The median time to ≥ Gr 2 onset was 15.5 days, the incidence of new stomatitis (Gr ≥ 2) plateaued at 6 wks. In a meta-analysis, 89% of first stomatitis events occurred within 8 wks. Topical steroids are used to treat aphthous ulcers; anecdotal use as prophylaxis has been reported. Methods: Eligibility included PM women with HR+ MBC prescribed EVE/EXE. Treatment included EVE 10 mg and EXE 25 mg QD, with 10 mL of commercially available 0.5 mg/5 mL dexamethasone oral solution to swish x 2 min, and spit QID for 8 wks, starting day 1. Pts completed a daily adherence log, including an oral pain (range 0-10) and normalcy of diet score. The primary endpoint was to compare the incidence of Gr ≥ 2 stomatitis at 8 wks with BOLERO-2 results. Secondary endpoints included: MW use by average times/day, EVE/EXE dose intensity, incidence of all Gr stomatitis and time to resolution to Gr ≤ 1. Results: 92 women were enrolled; 86 are evaluable for efficacy. Median age was 61 yrs (range 34-87); 38% were treated with EVE/EXEin the ≥ 2nd-line setting. Median dose intensity was 10 (range 3-14) and 25 mg (range 8-25) for EVE and EXE. 95% of pts used the MW 3-4 times/day (median MW use/d = 3.95, range 1.9-4). The rate of ≥ Gr 2 stomatitis at 8 weeks was 2.4% (2 pts) with a Gr 1 rate of 17.4%; there were no ≥ Gr 3 events. A comparison of stomatitis incidence by grade between BOLERO-2 and SWISH is shown in the Table. Mean pain scale score was < 1 at all visits; 86% of pts reported a normal diet at 8 wks. 12% discontinued EVE/EXE due to suspected related adverse events (most common: rash [2%], hyperglycemia [2%], stomatitis [1%] and pneumonitis [1%]). Conclusions: Prophylactic use of 0.5 mg/5 mL dexamethasone oral solution markedly decreases 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. Clinical trial information: NCT02069093.Study Stomatitis Grade (%) All 1 2 3 4 BOLERO-2 (total) 67 34 25 8 0 SWISH (at 8 weeks) 19.8 17.4 2.4 0 0