Breast cancer treatment with everolimus and exemestane for ER-positive women: the 2nd interim analysis of the BRAWO trial
In the pivotal phase 3 BOLERO-2 trial, the combination of everolimus (EVE) with exemestane (EXE) more than doubled median progression-free survival (PFS) versus placebo (PBO) with EXE in postmenopausal women with hormone-receptor positive (HR+) advanced breast cancer who were progressing after a nonsteroidal aromatase inhibitor (7.8 vs. 3.2 months; HR: 0.45; p < 0.0001). The BRAWO trial presented here is a large, German, non-interventional study (NIS) with a planned enrollment of 3,000 patients with HR+ advanced breast cancer receiving EVE+EXE. The main objectives of this study are to extend the knowledge on the efficacy, the impact of physical activity on efficacy, quality of life under routine conditions, prophylaxis and management of stomatitis, and the most optimal sequence of therapy and drug utilization, when EVE+EXE is used in usual daily care. During ESMO 2014 the second preplanned interim analysis of BRAWO was presented with efficacy data on EVE+EXE under real-world conditions.
All patients with HR+ advanced breast cancer receiving EVE+EXE treated in accordance with EVE labeling text are eligible for inclusion in BRAWO (planned N = 3,000). As such, the BRAWO trial population will be broader than the BOLERO-2 study (e.g. previous EXE therapy and more than 1 previous chemotherapy for the palliative setting are allowed). In total, 1,348 patients had entered study documentation through 19th of August 2014. This second interim analysis includes data of the first 500 patients.
The median time from primary diagnosis was 7.2 years and the median time from first diagnosis of recurrence/metastases was 2.7 years. In total 53.7% of patients had visceral metastases at baseline, 43.6% of patients had ECOG performance status 0 at baseline and 86.7% of patients received 10 mg EVE at the start of therapy.
Most patients received EVE+EXE as first-line (131 patients, 26.2%) or second-line (144 patients, 28.8%) treatment for advanced disease. Most patients (n=445, 89.0%) switched to EVE+EXE because of disease progression under a previous therapy. For patients receiving EVE+EXE in the advanced setting as first- or second-line therapy, letrozole and anastrozole were the most common last prior antineoplastic therapies.
The median PFS observed with the first 500 patients was 8.0 months, while the median PFS observed in the subset of patients who received EVE+EXE as first-line therapy for advanced disease (n = 131) was 10.1 months. Adverse events (AEs) observed in BRAWO were consistent with that previously reported with EVE+EXE in patients with advanced breast cancer. The most commonly reported AEs of any grade reported in ≥ 10% of patients were stomatitis (39.8%), fatigue (15.6%), diarrhea (13.2%), dyspnoe (13.0%), nausea (12.0%) and decreased appetite (10.4%). In total, 48.1% of patients required EVE dose reduction during therapy. Most treatment interruptions were implemented because of adverse events.
In summary, compared with BOLERO-2, patients in the BRAWO trial were older (66 vs. 62 years, respectively) and a smaller percentage of patients had an ECOG PS of 0 (43.6% vs 60%, respectively). The percentages of patients with visceral metastases were comparable in BRAWO and BOLERO-2 (53.7% vs. 58%, respectively). The median PFS in BRAWO was consistent with BOLERO-2 in the overall population (8.0 months and 7.8 months, respectively) and in patients receiving EVE+EXE as first-line therapy in the advanced setting (10.1 months and 11.5 months, respectively). Also the overall safety profile observed in the BRAWO study was comparable to that observed in BOLERO-2 and reported with EVE in other cancer indications. However, the percentage of patients with any grade stomatitis was lower in BRAWO (39.8%) compared with BOLERO-2 (59%), probably related to the fact that 86.8% of patients received prophylactic stomatitis treatment in BRAWO.
Fasching A, Decker T, Schneeweis A et al. Breast cancer treatment with Everolimus and Exemestane for ER-positive Women: the 2nd interim analysis of the non-interventional trial, BRAWO. Presented at ESMO 2014; Abstract LBA9.