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: 2ndinterim analysis from STEPAUT

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. 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, Ohler 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.