Everolimus Benefit Suggested for HR-Negative, HER2-Positive Advanced Breast Cancer

Everolimus may offer additional progression-free survival to hormone receptor-negative, HER2-positive patients with breast cancer undergoing trastuzumab and paclitaxel treatment

medwireNews: BOLERO-1 trial results suggest that select patients with advanced breast cancer may derive a progression-free survival (PFS) benefit from the addition of everolimus to first-line trastuzumab and paclitaxel therapy.

PFS did not significantly differ between treatment groups in the overall BOLERO-1 population of patients, but among the 311 patients with hormone receptor (HR)-negative, HER2-positive breast cancer given trastuzumab plus paclitaxel, there was a trend towards longer PFS in patients randomly assigned to receive everolimus versus placebo, at a median of 20.27 versus 13.08 months.

“[T]he 7·2 months prolongation we noted with the addition of everolimus in the HR-negative, HER2-positive population warrants further investigation, even if it did not meet prespecified criteria for significance”, write Sara Hurvitz, from the University of California, Los Angeles in the USA, and co-workers.

The safety profile was consistent with that reported by the BOLERO-3 investigators, the researchers add, with 86% of everolimus-treated patients requiring a dose interruption or reduction compared with 74% of placebo-treated patients.

Neutropenia and stomatitis were the most commonly reported grade 3 or 4 side effects by everolimus-treated patients, while anaemia and neutropenia were among the most frequent in the placebo group. Deaths associated with adverse events during treatment occurred in 4% of everolimus group versus none of the placebo group.

“Proactive monitoring and early management of adverse events are warranted in patients receiving this combination regimen”, the researchers emphasise in The Lancet Oncology.

The author of an accompanying comment suggests that replacing paclitaxel and trastuzumab with the “better tolerated” trastuzumab emtansine might be a “more feasible option” for patients undergoing treatment with everolimus or the newer PI3K inhibitors.

“Taken together, both BOLERO-1 and BOLERO-3 strongly support the hypothesis that mTOR inhibition has different effects in HR-negative and HR-positive HER2-positive breast cancer”, writes Gunter von Minckwitz, from GBG Forschungs GmbH in Neu-Isenburg, Germany.

He concludes: “[D]espite the formally negative outcome of BOLERO-1, the trial’s results support the idea that HER2-positive disease is a super family of disease, composed of various subgroups that can be discriminated at least by HR status and possibly also by PI3K mutation status, providing further insights into the development of further subgroup-specific treatment approaches.”


Hurvitz SA, Andre F, Jiang Z, et al. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol; Advance online publication 16 June 2015. DOI: dx.doi.org/10.1016/S1470-2045(15)00051-0

Von Minckwitz G. A step towards a HER2-positive breast cancer super family. Lancet Oncol; Advance online publication 16 June 2015. DOI: dx.doi.org/10.1016/S1470-2045(15)00037-6

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