Abstract P1-15-06: Evaluation of miracle mouthwash (MMW) plus hydrocortisone versus prednisolone mouth rinses as prophylaxis for everolimus-associated stomatitis: Preliminary results of a randomized phase II study
Authors: Jones VL , Jensen LL , McIntyre KJ , Oommen SP , Patt DA , Cortas TE , Harris RP , Wilks ST , Fox P , O'Shaughnessy JA 
Published: May 2016

Background: Oral stomatitis is a frequent adverse event (AE) associated with mTOR-inhibitor therapy, and can impact treatment adherence. In the BOLERO-2 trial in patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (MBC) treated with exemestane (EXE) plus everolimus (EVE), the incidence of all-grade stomatitis or related AEs was 67%, with 24% and 8% of pts developing Grade (G) 2 and G3 stomatitis or related AEs, respectively (Perez et al ASCO 2013 Abst 7029). In BOLERO-2, 24% of pts required EVE dose reduction for stomatitis (Rugo et al Ann Oncol 2014;25:808). The current study evaluated 2 different steroid-based mouth rinses for the prevention or amelioration of oral stomatitis in pts with MBC treated with EVE. Methods: This prospective randomized phase II study enrolled postmenopausal pts (planned accrual=100) with HR+ MBC within the US Oncology Network who were initiating therapy with an aromatase inhibitor plus EVE (10 mg/day). Eligible pts were randomized, blinded, 1:1 to prophylactic treatment with 1 of 2 oral rinses (ARM 1: MMW 480 ml recipe: 320 mL oral Benadryl, 2 g Tetracycline, 80 mg Hydrocortisone, 40 mL Nystatin suspension, water; or ARM 2: Prednisolone 15mg/5mL oral solution). Pts were instructed to swish/expectorate 10 ml of the assigned rinse 4 x daily starting with Day 1 of EVE treatment, for a total of 12 wks. The primary objective was to determine the incidence of G≥2 stomatitis during the first 12 wks of treatment. Secondary objectives included assessment of AEs (all grades), determination of the percentage of pts requiring dose interruption and/or dose reduction of EVE or discontinuation of therapy due to toxicity, and evaluation of the impact of the oral rinses on the duration and severity of stomatitis. Results: As of April 16, 2015, a total of 48 pts have been randomized and 47 pts have received treatment, with a mean time on mouth rinse of 68 days (range 2-84 days). Median age was 65 yrs (range 31-82 yrs). Twelve patients developed an oral AE and the incidence of all-grade stomatitis was 25% (n=12/48). The incidence of G1 stomatitis was 17% (8/48), G2 stomatitis was 8% (4/48) and there were no G3 events. The 4 G2 stomatitis AEs occurred within the first 30 days of treatment. One pt (1/48; 2%) required EVE dose delay. One pt developed oral candidiasis while on the steroid mouth rinse and no pts have stopped the steroid mouth rinse therapy due to mouth rinse-related toxicity. Conclusion: These preliminary data are the first from a prospective trial to provide evidence of a reduced incidence of mTOR-associated stomatitis with prophylactic use of a steroid mouth rinse. The 25% incidence of all-grade and 8%/0% incidence of G2/3 stomatitis compare favorably with the 67% and 24%/8% incidence of all-grade and G2/3 stomatitis, respectively, in BOLERO-2. These preliminary data also demonstrated the safety and tolerability of these 2 steroid mouth rinses. The incidence of stomatitis on each study arm will be available when accrual is completed. The prophylactic use of steroid mouth rinses substantially decreases the incidence of G2/3 stomatitis and the need for EVE dose interruption/reduction.

Citation Format: Jones VL, Jensen LL, McIntyre KJ, Oommen SP, Patt DA, Cortas TE, Harris RP, Wilks ST, Fox P, O'Shaughnessy JA. Evaluation of miracle mouthwash (MMW) plus hydrocortisone versus prednisolone mouth rinses as prophylaxis for everolimus-associated stomatitis: Preliminary results of a randomized phase II study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-15-06.