First-Line BOLERO-4 Results Reported For Everolimus Plus Letrozole in ER+/HER2– Breast Cancer

Early findings support use of everolimus with letrozole for patients with advanced, oestrogen receptor-positive, HER2–negative postmenopausal breast cancer

medwireNews: Preliminary BOLERO-4 results add to the evidence for first- and second-line use of everolimus plus letrozole in oestrogen receptor (ER)-positive, HER2-negative, advanced postmenopausal breast cancer previously treated only with nonsteroidal aromatase inhibitors (NSAIs).

The open-label phase II findings were reported at the ESMO 2016 Congress, held in Copenhagen, Denmark, by Melanie Royce, from the University of New Mexico Comprehensive Cancer Center in Albuquerque, USA.

The results included data for 202 patients who were treatment-naïve for locally advanced or metastatic breast cancer and given first-line everolimus 10 mg/day plus letrozole 2.5 mg/day. On disease progression, the patients were offered everolimus 10 mg/day plus exemestane 25 mg/day until further progression or unacceptable tolerability.

After a median of 17.5 months, the primary endpoint of progression-free survival (PFS) in the first line was not reached, the presenter said, with Kaplan–Meier estimated PFS at 6, 12 and 18 months of 83.6%, 71.4% and 59.5%, respectively.

The secondary endpoint of overall response rate in the first-line total population was 42.6% and the clinical benefit rate was 74.3%. In the 168 patients with measurable disease at baseline, the corresponding values were 51.8% and 75.9%.

This included a “rare” complete response in the overall and measureable disease groups in 1.5% and 1.8% of patients, respectively, and partial responses in 41.1% and 50.0%.

There were no new safety signals in the BOLERO-4 trial. But all patients experienced adverse events with first-line everolimus plus letrozole, with grade 3 affecting 36.1% and grade 4 affecting 4.5%. Serious study-related adverse events were reported in 10.4%, with grade 3 and 4 events leading to discontinuation in 6.4% and 2.5%, respectively.

Common grade 3 events with everolimus plus letrozole included anaemia (7.9%), stomatitis (6.4%) and weight loss (5.4%), with grade 4 hyperglycaemia in 1.0%, dyspnoea in 0.5%, and anaemia and hypertriglyceridaemia in 0.5% each.

“Given results from past studies (TAMRAD and BOLERO-2), BOLERO-04 results support the rationale for mTOR inhibition with everolimus in combination with various endocrine therapies for the treatment of postmenopausal women with [hormone receptor-positive advanced breast cancer]”, Melanie Royce said.

“BOLERO-4 results confirm that dual inhibition of signalling in ER+, HER2–[advanced breast cancer] is an effective treatment approach regardless of progression on prior NSAI therapy.”

The presenter concluded that the study is ongoing and additional second-line PFS results, overall survival results and substudy data for stomatitis will be reported at a later date.


ESMO 2016 Congress; Copenhagen, Denmark: 7–11 October

222O - BOLERO-4: Phase 2 trial of first-line everolimus (EVE) plus letrozole in estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (BC).

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