Abstract P2-11-08: Stomatitis in patients treated with first-line everolimus (EVE) plus letrozole (LET): Results from BOLERO-4 trial
Authors: C Villanueva, K Tsugawa, T Toyama, W Noh, J Jeong, F Cardoso, V Sriuranpong, V Srimuninnimit, M Ozguroglu, S Kendall, C Falkson, M Cianfrocca, C Manlius, JCJ Lin, F Ringeisen, A Ridolfi, M Royce
Journal: Cancer Research (2017)

Abstract Background Stomatitis is the most frequent adverse event reported in trials of mTOR-inhibitors, including EVE. In the pivotal phase 3 BOLERO-2 study, stomatitis incidence in the EVE + exemestane (EXE) arm was 59%. The BOLERO-4 study (NCT01698918) evaluated the efficacy and safety of first-line EVE + LET in postmenopausal pts with HR+, HER2− metastatic or locally advanced breast cancer (ABC). BOLERO-4 also assessed the effectiveness of an alcohol-free dexamethasone (0.5 mg/ 5ml; DEX) oral rinse for treating stomatitis in a subset of pts (USA). Methods Postmenopausal pts with HR+, HER2− ABC previously untreated for advanced disease received EVE (10 mg/day) + LET (2.5 mg/day).At disease progression, pts were offered EVE (10 mg/day) + EXE (25 mg/day). Pts who had at least one episode of stomatitis received oral stomatitis daily questionnaire (OSDQ), which is a 6 question pt-reported outcome (PRO) survey (Stiff et al, JCO. 2006). A subset of these pts (USA) was randomized (1:1) to receive DEX or standard of care (SOC). The primary objective of investigator-assessed progression-free survival in the first-line setting for ABC was presented previously. A secondary objective was to evaluate the effectiveness of the DEX oral rinse in reducing the severity and duration of stomatitis, using OSDQ data. Results Of the total 202 pts enrolled in this study, 52 pts were enrolled in USA, of which, 24 (46.2%) were randomized to receive DEX (n=11) or SOC (n=13), upon confirmation of stomatitis. The median duration of first stomatitis episode was longer per OSDQ (DEX, not estimable vs SOC, 13.7 wk) compared with physician-reported duration (DEX, 1.6 wk vs SOC, 1.9 wk). PRO OSDQ results were similar in both arms. Among the 202 pts enrolled, 89 (44.1%) filled the OSDQ at their first stomatitis episode. The median time from treatment initiation to first stomatitis episode was 1.7 wk; median duration of stomatitis was 13.7 wk (OSDQ) vs 2.1 wk (physician reported). The majority of pts experiencing stomatitis had moderate/little/no soreness, moderate/low/no pain, and stomatitis had low/no effect on daily activities (Table 1). Table 1. OSDQ Key Results (N=87)Questions (Score)First Day of Stomatitis Episode, n (%)End of First Stomatitis Episode, n (%)Overall healthPoor (0-4)20 (23.0)23 (26.4)Moderate (5-7)40 (46.0)32 (36.8)Perfect (8-10)27 (31.0)32 (36.8)Mouth and throat sorenessNo/a little/moderate (0-2)64 (73.6)84 (96.6)A lot or extreme (3-4)23 (26.4)3 (3.4)Mouth pain severityNo/low/moderate (0-4)51 (58.6)73 (83.9)Severe (5-7)24 (27.6)10 (11.5)Unbearable (8-10)12 (13.8)4 (4.6)Effect on daily activitiesNo/low (0-4)70 (80.5)78 (89.7)Moderate (5-7)11 (12.6)4 (4.6)High (8-10)6 (6.9)5 (5.7) Conclusions Overall, patient-reported median duration of stomatitis was longer than that reported by physicians, most likely due to differences in perceptions and the challenges in collecting and cleaning PRO data. Overall good health score was maintained in the majority of pts experiencing stomatitis and stomatitis had low/no effect on daily activities. However, these results, especially in the randomized subset need to be interpreted with caution owing to the small sample size, missing data and lack of commercially available DEX in most countries. Citation Format: Villanueva C, Tsugawa K, Toyama T, Noh W, Jeong J, Cardoso F, Sriuranpong V, Srimuninnimit V, Ozguroglu M, Kendall S, Falkson C, Cianfrocca M, Manlius C, Lin JCJ, Ringeisen F, Ridolfi A, Royce M. Stomatitis in patients treated with first-line everolimus (EVE) plus letrozole (LET): Results from BOLERO-4 trial [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 P2-11-08.