Abstract P4-22-20: Efficacy and safety of everolimus plus exemestane in HR+, HER2– advanced breast cancer progressing on/after prior endocrine therapy, in routine clinical practice: 2nd interim analysis from STEPAUT
Authors: Steger GG , Bartsch R , Pfeiler G , Petru E , Greil R , Helfgott R , Egle D , Öhler L , Lang A , Tinchon C , Haslbauer F , Redl A , Hennebelle M , Mraz B , Winiger-Candolfi I , Gnant M 
Published: March 2017

Abstract
Background
STEPAUT, an Austrian non-interventional study evaluated the safety and efficacy of everolimus (EVE) + exemestane (EXE) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2–) advanced breast cancer (ABC) recurring/progressing on/after prior nonsteroidal aromatase inhibitors (NSAIs) in routine clinical practice. Results of the 1st interim analysis (IA) were consistent with BOLERO-2 data. Here we present results from the 2nd pre-planned IA.
Materials and Methods
STEPAUT, with a planned enrolment of 300 pts, included postmenopausal pts, aged ≥ 18 yrs with HR+, HER2– ABC treated with EVE+EXE, progressing on/after NSAIs. Primary endpoint was progression-free survival (PFS); secondary endpoints included response per RECIST v1.1 and safety.
Results
The 2nd IA included 225 pts with a median age of 65 yrs. At the time of data cut-off: 9 May, 2016, 147 pts had discontinued study treatment, mainly due to disease progression and adverse events (AEs). Median duration of follow-up was 6.5 months (range 0−26.3 months), 172 pts (95%) had ECOG PS 0-1 and 52% of pts had visceral metastasis. A majority of pts (n=109, 54%) received the approved EVE dose of 10mg as the start dose, while 91 pts (45%) received half of the approved EVE dose i.e. 5mg. Median PFS values for different subgroups are shown in table 1 below. Overall, 57 pts (28%) required therapy interruption while 37 pts (18%) had EVE dose reduction from 10 to 5mg. A decreasing trend in AE frequency irrespective of EVE dose was observed during treatment period. The majority of AEs were of mild to moderate severity; most frequent AEs (all grades) were stomatitis, mucositis (48.0%), exanthema, rash (22.2%), and dyspnea, cough (22.2%). Frequent grade 3 or 4 AEs were stomatitis, mucositis (4.4%), weight loss, reduced general condition (2.7%), and inappetence, nausea (2.2%). Median time to first occurrence of stomatitis was 0.5 months; 8 pts (5%) discontinued therapy due to stomatitis and/or rash. Serious AEs constituted 10% of all AEs.
Table 1: Median PFS across various subgroups PFS (months)95% Confidence intervalOverall (n=206)9.57.7-10.7DoseEVE 10mg (n=68)9.16.4-10.7EVE 5mg (n=53)6.53.7-12.5EVE 5 to 10mg (n=17)11.35.4-15.4EVE 10 to 5mg (n=27)9.57.7-14.7Therapy linesFirst* (n=12)11.3#8.4-14.2Second (n=24)11.311.3-11.3Third (n=25)13.36.5-23.7Fourth (n=14)10.05.5-10.0Fifth and beyond (n=11)7.35.6-8.7Stomatitis and/or rash incidenceStomatitis (n=73)9.15.5-11.9Rash (n=16)9.23.4-18.4Stomatitis and rash (n=34)11.510.3-19.0*only 2 events, #mean value
Conclusions
Real world data from STEPAUT support EVE+EXE as a suitable treatment option for HR+, HER2− ABC recurring or progressing on/after prior NSAIs. Overall safety profile was also consistent with previous reports. Of note, occurrence of stomatitis and/or rash did not negatively influence PFS. Furthermore, a lower start dose of EVE 5mg did not seem to affect PFS negatively as long as the dose was adjusted to 10mg after a short period of time, thus supporting the administration of the approved EVE 10mg/day dose in the routine clinical setting.
Citation Format: Steger GG, Bartsch R, Pfeiler G, Petru E, Greil R, Helfgott R, Egle D, Öhler L, Lang A, Tinchon C, Haslbauer F, Redl A, Hennebelle M, Mraz B, Winiger-Candolfi I, Gnant M. Efficacy and safety of everolimus plus exemestane in HR+, HER2– advanced breast cancer progressing on/after prior endocrine therapy, in routine clinical practice: 2nd interim analysis from STEPAUT [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 P4-22-20.