Abstract P4-13-08: Stomatitis in patients treated with everolimus and exemestane - Results of the 3rd interim analysis of the non-interventional trial BRAWO
Authors: Schütz F , Grischke E-M , Decker T , Uleer C , Schneeweiss A , Salat C , Wimberger P , Mundhenke C , Förster F , Kluth-Pepper B , Schubert J , Bloch W , Tesch H , Jackisch C , Lüftner D , Fasching PA 
Published: May 2016

Abstract
Background
BRAWO is a German non-interventional study of 3000 patients (pts) with advanced/metastatic, hormone receptor positive and HER2 negative breast cancer treated with everolimus and exemestane (EVE+EXE). One of the objectives was the documentation of how stomatitis was managed and prevented in clinical routine. We report data of the 3rd preplanned interim analysis (IA) focusing on prophylaxis and management of stomatitis in daily clinical routine.
Methods
Here we report data of the first 1300 documented pts on efficacy and safety with focus on the adverse event stomatitis. Patient and treatment characteristics were associated with the occurrence of stomatitis. Furthermore chosen treatments for the management of stomatitis are described.
Results
At time of data cut-off 71% pts had discontinued the study, 29% were still under therapy. Patient and tumor characteristics were reported previously. The most commonly reported AEs of any grade were stomatitis (41.5%), fatigue (14.6%), nausea (12.2%), diarrhea (12.1%), dyspnea (11.3%). 75.2% of stomatitis events occurred during the first 5 weeks of treatment, regardless of the chosen starting dose 5 mg or 10 mg EVE per day. Median duration of a stomatitis episode was 28 days for 5 mg EVE start dose and 23 days for 10mg. However, there was a numerically lower stomatitis incidence and less severe intensity of stomatitis for a start dose of 5 mg vs 10 mg (Table 1).
Table 1: Stomatitis incidence and severity by EVE start dose:
Worst intensitiy of stomatitisTotal (n=1300)Start dose 5mg (n=316)Start dose 10mg (n=975)Other* (n=9)Number (%) of pts with at least one stomatitis event (any grade)513 (41.5)115 (36.4)421 (43.2)3 (33.3)Grade 1276 (21.2)73 (23.1)202 (20.7)1 (11.1)Grade 2198 (15.2)31 (9.8)165 (16.9)2 (22.2)Grade 330 (2.3)3 (0.9)27 (2.8)0Unknown35 (2.7)8 (2.5)27 (2.8)0*Other includes 2.5mg (n=3), 7.5mg (n=2), 15mg (n=1), 20mg(n=2), 30mg (n=1)
86.5% of pts received recommendations regarding stomatitis prophylaxis. The most frequent recommendations were: mild dental hygiene (e.g. soft toothbrush) (74.8%), avoidance of hot, sour or salty food (70.9%), rinsing with tea (61.7%), and cooling (e.g. sucking ice or frozen pineapple) (56,6%).
At least one therapeutic measure was documented for 85.5% of stomatitis events. The most common therapeutic measures were non-drug mouthwash solution (58.3%), cooling (34.7%) or drug intervention (31.9%). Temporary EVE dose adjustments due to stomatitis were done in 11.6% of stomatitis events, temporary dose interruptions in 21.8%, respectively.
Efficacy of EVE+EXE seemed to be independent of stomatitis occurrence within 8 weeks after therapy start: mPFS 6.9 months (95%CI, 6.4-8.0) without stomatitis, mPFS 7.4 months (95%CI, 6.3-8.6) with stomatitis.
Discussion
The percentage of patients with any grade stomatitis was lower in BRAWO (41.5%) than in the pivotal BOLERO-2 trial (59%), which might be explained by increased awareness and experience of treating physicians for prophylaxis and management of this type of adverse event under treatment with EVE+EXE. Most stomatitis events occurred during the first 5 weeks of treatment, which is consistent with data from BOLERO-2.
Citation Format: Schütz F, Grischke E-M, Decker T, Uleer C, Schneeweiss A, Salat C, Wimberger P, Mundhenke C, Förster F, Kluth-Pepper B, Schubert J, Bloch W, Tesch H, Jackisch C, Lüftner D, Fasching PA. Stomatitis in patients treated with everolimus and exemestane - Results of the 3rd interim analysis of the non-interventional trial BRAWO. [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 P4-13-08.