Abstract P4-22-17: Safety of the combination of everolimus plus exemestane in the Italian cohort of patients enrolled in the expanded access “BALLET” study
Authors: Generali D , Bordonaro R , Febbraro A , Madoffa A , Romito S , Michelotti A , Savastano C , Mariani G , Tondini C , Piovano P , Iona MT , Bighin C , Roviello G , Ascione G , Goffredo F , Sartori D , Frassoldati A , Simoncini E 
Published: March 2017

Abstract
Background:The expanded access “BALLET” study has been designed toevaluate the safety of EVE plus EXE combination in hormone receptor-positive (HR+), human epidermal growth factor-receptor-2-negative (HER2-) metastatic Breast Cancer (mBC). The Italian population was predominantly enrolled in trial.
Patients and methods: Patients has been included according to the inclusion and exclusion criteria provided previously in the BALLET study. The aim of our analysis was the safety everolimus and exemestane analysed in two sets of population: a subpopulation including only patients who never received chemotherapy in metastatic setting (416 patients – 36.1% of the safety population) and a subpopulation including only patients who received at least one chemotherapy in metastatic setting, whatever the line of treatment (735 patients – 63.9%).
Results:One thousand two hundred seventy nine (1279) Italian female patients were screened, 1153 (90.1% of the screened set) out of these were included in the analysis and 1151 (90.0% of the screened set) were included in the safety population. 1116 (97.0% of the safety population) prematurely discontinued the study drug and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%) and adverse event(s) (16.1%). The mean duration of study treatment exposure was 158.3±106.79 days (median 139.5) for exemestane and 153.9±108.48 days (median 135.0) for everolimus with a treatment compliance (higher than 90%) of 94.4% and 58.6% and (lower than 60%) of 0.1% and 15.1% for exemestane and everolimus, respectively. 92.5% of patients of the safety population (91.1% and . 93.3% patients without and with chemotherapy respectively) experienced at least one adverse event: gastrointestinal disorders” (67.3% vs. 64.6% in without and with chemo group); general disorders (48.6% vs. 48.3%); metabolism and nutrition disorders (35.6% vs. 37.4%) and skin and subcutaneous tissue disorders (32.2% vs. 27.5%). The incidence of everolimus related adverse events was higher (83.9%) when compared to those which occurred with exemestane. The most commonly reported adverse event was stomatitis (51.3% of patients) with 22.5% Grade 1; 18.2% Grade 2; 10.5% Grade 3; 0.2% Grade 4. The 49.7% of the patients experienced at least one stomatitis related to everolimus. No relevant difference was observed between the two groups of patients without and with chemo in metastatic setting.
Conclusions: The administration of chemotherapy before starting EVE plus EXE combination did not affect the safety profile of EXE/EVE in the treatment of mBC. The stomatitis is the most frequent and relevant adverse event to be clinically focused on.
Citation Format: Generali D, Bordonaro R, Febbraro A, Madoffa A, Romito S, Michelotti A, Savastano C, Mariani G, Tondini C, Piovano P, Iona MT, Bighin C, Roviello G, Ascione G, Goffredo F, Sartori D, Frassoldati A, Simoncini E. Safety of the combination of everolimus plus exemestane in the Italian cohort of patients enrolled in the expanded access “BALLET” 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 P4-22-17.