Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1.

Abstract

BACKGROUND:

The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial.

METHODS:

Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR-) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety.

RESULTS:

In the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61-1.11)). In the HR- subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29-0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm.

CONCLUSIONS:

The efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT00876395 . Registered on 2 April 2009.

• Authors: Masakazu Toi, Zhimin Shao, Sara Hurvitz, Ling-Ming Tseng, Qingyuan Zhang, Kunwei Shen, Donggeng Liu, Jifeng Feng, Binghe Xu, Xiaojia Wang, Keun Seok Lee, Ting Ying Ng, Antonia Ridolfi, Florence Noel-Baron, Francois Ringeisen, Zefei Jiang
• Journal: Breast cancer research : BCR (Breast Cancer Res) Vol. 19 Issue 1 Pg. 47 (04 11 2017) ISSN: 1465-542X [Electronic] England
• PMID: 28399902 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Everolimus
• Receptor, ErbB-2
• Trastuzumab
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, mortality, pathology)
• Everolimus (administration & dosage)
• Female
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Paclitaxel (administration & dosage)
• Proportional Hazards Models
• Receptor, ErbB-2 (metabolism)
• Retreatment
• Trastuzumab (administration & dosage)
• Treatment Outcome
• Young Adult