Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

Abstract

INTRODUCTION:

Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population.

METHODS:

BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints.

RESULTS:

Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31-0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, [corrected] and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials.

CONCLUSION:

The addition of everolimus to exemestane markedly prolonged PFS in patients with HR(+) advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

• Authors: Denise A Yardley, Shinzaburo Noguchi, Kathleen I Pritchard, Howard A Burris 3rd, José Baselga, Michael Gnant, Gabriel N Hortobagyi, Mario Campone, Barbara Pistilli, Martine Piccart, Bohuslav Melichar, Katarina Petrakova, Francis P Arena, Frans Erdkamp, Wael A Harb, Wentao Feng, Ayelet Cahana, Tetiana Taran, David Lebwohl, Hope S Rugo
• Journal: Advances in therapy (Adv Ther) Vol. 30 Issue 10 Pg. 870-84 (Oct 2013) ISSN: 1865-8652 [Electronic] United States
• PMID: 24158787 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Receptors, Estrogen
• Receptors, Progesterone
• Everolimus
• exemestane
• Sirolimus

Topics

• Adult
• Aged
• Aged, 80 and over
• Androstadienes (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bone Neoplasms (drug therapy, secondary)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Disease-Free Survival
• Double-Blind Method
• Everolimus
• Female
• Humans
• Liver Neoplasms (drug therapy, secondary)
• Lung Neoplasms (drug therapy, secondary)
• Middle Aged
• Postmenopause
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Sirolimus (administration & dosage, analogs & derivatives)
• Treatment Outcome