Abstract P4-16-01: Evaluation of miracle mouthwash (MMW) plus hydrocortisone or prednisolone mouth rinses as prophylaxis for everolimus-associated stomatitis: Results of a randomized phase II study
Authors: Jones VE , McIntyre KJ , Paul D , Wilks ST , Ondreyco SM , Sedlacek SM , Melnyk AM , Oommen SP , Wang Y , O'Shaughnessy JA 
Published: March 2017

Abstract
Background: Oral stomatitis is a frequent adverse event (AE) associated with mTOR-inhibitor therapy, and can impact adherence. In BOLERO-2, patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (MBC) treated with exemestane plus everolimus (EVE), the incidence of all-grade (G) stomatitis or related AEs was 67%, with 24%/8% of pts developing G2/G3 stomatitis or related AEs, respectively (Perez et al ASCO 2013 Abs 7029). In BOLERO-2, 24% of pts required EVE dose reduction for stomatitis (Rugo et al Ann Oncol 2014;25:808). This study evaluated 2 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)(AIE). Pts were randomized 1:1 to prophylactic therapy 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 (P) 15mg/5mL oral solution, 1.8% alcohol). Pts were instructed to swish/expectorate 10 ml of the assigned rinse 4x daily starting with D1 of EVE treatment, for a total of 12 wks. The primary objective was to determine the incidence of G≥2 stomatitis or related oral AEs during the first 12 wks of treatment. Based on a historical estimate that ≥37% of pts receiving AIE develop G≥2 stomatitis, 50 pts for each arm were required to detect a reduction of the incidence of G≥2 stomatitis from 37% to &lt;20%, with alpha = 0.05, 80% power, and a 1-sided test. Secondary objectives included assessment of AEs (all grades), determination of the percentage of pts requiring dose interruption/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 5/30/2016, a total of 104 pts have been randomized and 100 pts have received treatment (49 MMW; 51 P). Median age was 61 yrs (range 31-82 yrs). The incidence of stomatitis and related oral AEs (any grade) during the first 12 wks was 29% (n=14/49) and 27.5% (14/51) in the MMW and P arms respectively. The incidence of G2 oral AEs was 12% (6/49) and 8% (4/51) with MMW and P respectively. There was only 1 G3 oral AE (MMW arm), and no G4 events. There was 1 EVE dose reduction (MMW) and 4 EVE dose delays (3 MMW, 1 P) during the first 12 wks of treatment. No pts stopped the steroid mouth rinse therapy due to mouth rinse-related toxicity. Conclusion: These prospective data provide evidence of a reduced incidence of mTOR-associated oral AEs with prophylactic use of a steroid mouth rinse. The 29%/27.5% incidence of all-grade and 12%/8% incidence of G2 oral AEs, with only 1 G3 event, compare favorably with the 67% and 24%/8% incidence of all-grade and G2/3 stomatitis, respectively, in BOLERO-2. These data also show the safety and tolerability of these 2 steroid mouth rinses. Prophylactic use of steroid mouth rinses substantially decreases the incidence of G2/3 stomatitis and the need for EVE dose modifications.
Citation Format: Jones VE, McIntyre KJ, Paul D, Wilks ST, Ondreyco SM, Sedlacek SM, Melnyk Jr. AM, Oommen SP, Wang Y, O'Shaughnessy JA. Evaluation of miracle mouthwash (MMW) plus hydrocortisone or prednisolone mouth rinses as prophylaxis for everolimus-associated stomatitis: Results of a randomized phase II study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-16-01.