STEPAUT trial confirms BOLERO-2 data

The real world data from STEPAUT confirm the BOLERO-2 data and support everolimus plus exemestane as a suitable treatment option for patients with HR+/HER2- advanced breast cancer recurring or progressing on or after prior nonsteroidal aromatase inhibitors. Up to 75% of breast cancers express the oestrogen receptor or progesterone receptor (hormone-receptor [HR]–positive). Endocrine therapy is the standard of care for postmenopausal women with advanced/metastatic breast cancer that is HR-positive and HER2-negative, with aromatase inhibitors being the preferred first-line treatment option. However, in the majority of patients, resistance to currently available options eventually develops, which requires the administration of sequential therapy with alternative endocrine regimens. This prompted the identification of effective treatment options that prolong or restore sensitivity to endocrine therapies.

In the pivotal BOLERO-2 trial, everolimus plus exemestane more than doubled median progression-free survival in HR+/HER2- advanced breast cancer recurring or progressing on or after prior non-steroidal aromatase inhibitors.

STEPAUT, an Austrian non-interventional study evaluated the safety and efficacy of everolimus plus exemestane in patients with HR+/ HER2– advanced breast cancer recurring or progressing on or after prior nonsteroidal aromatase inhibitors in routine clinical practice. STEPAUT, with a planned enrolment of 300 patients, included postmenopausal patients, aged > 18 years with HR+/HER2- advanced breast cancer treated with everolimus plus exemestane, progressing on or after nonsteroidal aromatase inhibitors. Primary endpoint was progression-free survival, secondary endpoints included response per RECIST v1.1 and safety.

Results of the first interim analysis were consistent with BOLERO-2 data. At the San Antonio Breast Cancer Conference results from the second pre-planned interim analysis were presented. The second interim analysis included 225 patients with a median age of 65 years. At the time of data cut-off (9 May, 2016), 147 patients had discontinued study treatment, mainly due to disease progression and adverse events. Median duration of follow-up was 6.5 months (range 0-26.3 months), 172 patients (95%) had ECOG PS 0-1 and 52% of patients had visceral metastasis. A majority of patients (N=109, 54%) received the approved everolimus dose of 10 mg as the start dose, while 91 patients (45%) received half of the approved everolimus dose i.e. 5 mg.

Median progression-free survival values for different subgroups are shown in keyslide 2. Overall, 57 patients (28%) required therapy interruption while 37 patients (18%) had everolimus dose reduction from 10 to 5 mg. A decreasing trend in adverse events frequency irrespective of everolimus dose was observed during treatment period. The majority of adverse events were of mild to moderate severity; most frequent adverse events (all grades) were stomatitis, mucositis (48.0%), exanthema, rash (22.2%), and dyspnoea, cough (22.2%). Frequent grade 3 or 4 adverse events 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 patients (5%) discontinued therapy due to stomatitis and/or rash. Serious adverse events constituted 10% of all adverse events.

In summary: these real world data from STEPAUT confirm the BOLERO-2 data and support everolimus plus exemestane as a suitable treatment option for patients with HR+/HER2- advanced breast cancer recurring or progressing on or after prior nonsteroidal aromatase inhibitors. Overall safety profile was also consistent with previous reports. Of note, occurrence of stomatitis and/or rash did not negatively influence progression-free survival. Furthermore, a lower start dose of everolimus (5 mg) did not seem to affect progression-free survival negatively as long as the dose was adjusted to 10 mg after a short period of time, thus supporting the administration of the approved everolimus 10 mg/day dose in the routine clinical setting.

Reference

Steger GG G, Bartsch R, Pfeiler G, et al. 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. Poster presentation at the San Antonia Breast Cancer Congress 2016. Abstract P4-22-20.