Abstract P6-18-08: Everolimus + exemestane for HR+ advanced breast cancer in routine clinical practice- Final results from the non-interventional trial, BRAWO

Abstract

Background: In the pivotal BOLERO-2 trial, everolimus (EVE) + exemestane (EXE) more than doubled the median progression-free survival (PFS) vs EXE alone in hormone receptor positive (HR+), human epidermal growth factor-receptor 2-negative (HER2-) advanced breast cancer (ABC) recurring/progressing on/after prior non-steroidal aromatase inhibitors (NSAIs). BRAWO is a German non-interventional study conducted in patients (pts) with HR+, HER2–ABC receiving EVE + EXE, according to Summary of Product Characteristics (SmPC), in routine clinical practice. Here we report the final PFS and safety results. Methods: This multicenter study documented 2100 pts between October 2012 and December 2017 across 341 sites in Germany. Postmenopausal women with HR+, HER2– ABC with recurrence or progression after a NSAI were included. Primary observation parameters included the evaluation of the effectiveness of EVE + EXE used in routine care for the entire pt group. Results: In the final analysis, out of the 2100 documented pts, 2074 were included in the full analysis set. The median time since the primary diagnosis was 7.1 years and the median time from first sign of relapse (local recurrence or distant metastases) was 2.1 years. At baseline, 54.1% of pts presented with visceral metastases and 50.1% had an ECOG performance status of 0. Approximately, 63% of pts started with EVE 10 mg (median duration of exposure: 5.1 months; 95% CI, 4.6-5.4), while 34.1% started with EVE 5 mg (median duration of exposure: 4.6 months; 95% CI, 4.1-5.2). The distribution of treatment lines was as follows: first line, 28.7% (n=595); second line, 31.9% (n=662); third line, 18.1% (n=376); fourth line, 10.7% (n=221) and, fifth line and later, 10.6% (n=220). Treatment was discontinued by 55.7% of pts (n=1170) due to progressive disease and 26% of pts (n=546) due to adverse events. The Kaplan-Meier estimate of the median PFS was 6.6 months (95% CI, 6.2-7.0). The best overall responses, based on clinical routine, were complete response, 0.8% (n=17), partial response, 7.4% (n=150), and stable disease, 41.3% (n=842). The general safety profile was consistent with the previously reported safety findings. The most common adverse events were stomatitis (any grade: 42.6%, grade 3: 3.8%, grade 4: <0.1%) and fatigue (any grade: 19.8%, grade 3: 1.5%). Conclusions: Data from BRAWO support EVE + EXE as a suitable treatment option with a reasonable safety profile for HR+, HER2− ABC recurring or progressing on/after prior NSAIs. Citation Format: Lüftner D, Schuetz F, Schneeweiss A, Grischke E-M, Bloch W, Decker T, Uleer C, Salat C, Förster F, Schmidt M, Mundhenke C, Tesch H, Jackisch C, Fischer T, Guderian G, Hanson S, Fasching P. Everolimus + exemestane for HR+ advanced breast cancer in routine clinical practice- Final results from the non-interventional trial, BRAWO [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-08.

A multicentre, randomised, double-blind, phase II study to evaluate the tolerability of an induction dose escalation of everolimus in patients with metastatic breast cancer (DESIREE)

“… 7 A similar rate of high-grade stomatitis was reported in other studies investigating everolimus plus exemestane in patients with HR-positive/HER2-negative advanced BC. 8 , 9 , 10 Real-world safety and efficacy data on everolimus in combination with exemestane were also consistent with the results from BOLERO-2. 11 , 12 …”

“…The starting dose, however, did not impact progression-free survival. 9 , 28 These results suggest that patients in routine clinical practice are sometimes treated with a dose-escalation schema of everolimus to allow the patient’s organism to adapt to the therapy.…”

Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications

“…Altogether, real-world data corroborate the efficacy of Eve in combination with ET for the treatment of HR+ HER2− mBC. Subgroup analyses of these studies indicate that ORR and PFS may be lower in patients treated with a higher number of previous therapy lines, with previous exposure to chemotherapy, or treated with lower Eve treatment intensity [38][39][40]. Finally, no ORR or PFS differences have been described based on prior treatment with Exe [38].…”

“…After the publication of the BOLERO-2 study, other prospective phase IIIb-IV trials (4EVER [38], BRAWO [39], STEPAUT [40], BALLET [41], EVEREXES [42]) investigated the efficacy and tolerability of Eve/Exe in more heterogeneous patient cohorts when compared to patients enrolled in the BOLERO-2 trial (Table 4) [8]. In particular, the 4EVER, BRAWO, and BALLET studies enrolled patients independently of the number of previous chemotherapy lines for advanced disease, as well as of previous Exe treatment, thus more faithfully recapitulating patients treated in the real-world clinical practice [38,39,41]. For instance, 60% and 53.7% of patients in the BALLET and 4EVER studies, respectively, had received previous chemotherapy for advanced disease when compared to 26% of patients in the BOLERO-2 study.…”