4 research outputs found
Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer: The BOLERO-6 Randomized Clinical Trial.
Importance: Everolimus plus exemestane and capecitabine are approved second-line therapies for advanced breast cancer. Objective: A postapproval commitment to health authorities to estimate the clinical benefit of everolimus plus exemestane vs everolimus or capecitabine monotherapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Design: Open-label, randomized, phase 2 trial of treatment effects in postmenopausal women with advanced breast cancer that had progressed during treatment with nonsteroidal aromatase inhibitors. Interventions: Patients were randomized to 3 treatment regimens: (1) everolimus (10 mg/d) plus exemestane (25 mg/d); (2) everolimus alone (10 mg/d); and (3) capecitabine alone (1250 mg/m2 twice daily). Main Outcomes and Measures: Estimated hazard ratios (HRs) of progression-free survival (PFS) for everolimus plus exemestane vs everolimus alone (primary objective) or capecitabine alone (key secondary objective). Safety was a secondary objective. No formal statistical comparisons were planned. Results: A total of 309 postmenopausal women were enrolled, median age, 61 years (range, 32-88 years). Of these, 104 received everolimus plus exemestane; 103, everolimus alone; and 102, capecitabine alone. Median follow-up from randomization to the analysis cutoff (June 1, 2017) was 37.6 months. Estimated HR of PFS was 0.74 (90% CI, 0.57-0.97) for the primary objective of everolimus plus exemestane vs everolimus alone and 1.26 (90% CI, 0.96-1.66) for everolimus plus exemestane vs capecitabine alone. Between treatment arms, potential informative censoring was noted, and a stratified multivariate Cox regression model was used to account for imbalances in baseline characteristics; a consistent HR was observed for everolimus plus exemestane vs everolimus (0.73; 90% CI, 0.56-0.97), but the HR was closer to 1 for everolimus plus exemestane vs capecitabine (1.15; 90% CI, 0.86-1.52). Grade 3 to 4 adverse events were more frequent with capecitabine (74%; n = 75) vs everolimus plus exemestane (70%; n = 73) or everolimus alone (59%; n = 61). Serious adverse events were more frequent with everolimus plus exemestane (36%; n = 37) vs everolimus alone (29%; n = 30) or capecitabine (29%; n = 30). Conclusions and Relevance: These findings suggest that everolimus plus exemestane combination therapy offers a PFS benefit vs everolimus alone, and they support continued use of this therapy in this setting. A numerical PFS difference with capecitabine vs everolimus plus exemestane should be interpreted cautiously owing to imbalances among baseline characteristics and potential informative censoring. Trial Registration: ClinicalTrials.gov identifier: NCT01783444
The MAGIC survey in hormone receptor positive (HR+), HER2-negative (HER2-) breast cancer: When might multigene assays be of value?
Background: A modest proportion of patients with early stage hormone
receptor-positive (HR+), HER2-negative (HER2-) breast cancer benefit
from adjuvant chemotherapy. Traditionally, treatment recommendations are
based on clinical/pathologic criteria that are not predictive of
chemotherapy benefit Multigene assays provide prognostic and predictive
information that can help to make more informed treatment decisions. The
MAGIC survey evaluated international differences in treatment
recommendations, how traditional parameters are used for making
treatment choices, and for which patients treating physicians feel most
uncertain about their decisions.
Methods: The MAGIC survey captured respondents’ demographics, practice
patterns, relevance of traditional parameters for treatment decisions,
and use of or interest in using multigene assays. Using this
information, a predictive model was created to simulate treatment
recommendations for 672 patient profiles.
Results: The survey was completed by 911 respondents (879 clinicians, 32
pathologists) from 52 countries. Chemo-endocrine therapy was recommended
more often than endocrine therapy alone, but there was substantial
heterogeneity in treatment recommendations in 52% of the patient
profiles; approximately every fourth physician provided a different
treatment recommendation. The majority of physicians indicated they
wanted to use multigene assays clinically. Lack of
reimbursement/availability were the main reasons for non-usage.
Conclusions: The survey reveals substantial heterogeneity in treatment
recommendations. Physicians have uncertainty in treatment
recommendations in a high proportion of patients with intermediate risk
features using traditional parameters. In HR+, HER2- patients with early
disease the findings highlight the need for additional markers that are
both prognostic and predictive of chemotherapy benefit that may support
more-informed treatment decisions. (C) 2017 Published by Elsevier Ltd