Health‐related quality of life of patients with advanced breast cancer treated with everolimus plus exemestane versus placebo plus exemestane in the phase 3, randomized, controlled, BOLERO‐2 trial

Abstract

BACKGROUND:The randomized, controlled BOLERO-2 (Breast Cancer Trials of Oral Everolimus) trial demonstrated significantly improved progression-free survival with the use of everolimus plus exemestane (EVE þ EXE) versus placebo plus exemestane (PBO þ EXE) in patients with advanced breast cancer who developed disease progression after treatment with nonsteroidal aromatase inhibitors. This analysis investigated the treatment effects on health-related quality of life (HRQOL). METHODS: Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, HRQOL was assessed at baseline and every 6 weeks thereafter until disease progression and/or treatment discontinuation. The 30 items in 15 subscales of the QLQ-C30 include global health status wherein higher scores (range, 0-100) indicate better HRQOL. This analysis included a protocol-specified time to definitive deterioration (TDD) analysis at a 5% decrease in HRQOL versus baseline, with no subsequent increase above this threshold. The authors report additional sensitivity analyses using 10-point minimal important difference decreases in the global health status score versus baseline. Treatment arms were compared using the stratified log-rank test and Cox proportional hazards model adjusted for trial stratum (visceral metastases, previous hormone sensitivity), age, sex, race, baseline global health status score and Eastern Cooperative Oncology Group performance status, prognostic risk factors, and treatment history. RESULTS: Baseline global health status scores were found to be similar between treatment groups (64.7 vs 65.3). The median TDD in HRQOL was 8.3 months with EVE þ EXE versus 5.8 months with PBO þ EXE (hazard ratio, 0.74; P ¼.0084). At the 10-point minimal important difference, the median TDD with EVE þ EXE was 11.7 months versus 8.4 months with PBO þ EXE (hazard ratio, 0.80; P ¼.1017). CONCLUSIONS: In patients with advanced breast cancer who develop disease progression after treatment with nonsteroidal aromatase inhibitors, EVE þ EXE was associated with a longer TDD in global HRQOL versus PBO þ EXE. Cancer 2013;119:1908-15.

A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer

“…Based on data from the BOLERO-2 trial, the mTOR inhibitor everolimus (EVE) in combination with exemestane (EXE) was approved by the US Food and Drug Administration and European Medicines Agency to treat postmenopausal women with HR?ve/ HER2-ve advanced breast cancer that recurred or progressed during or after a non-steroidal AI therapy [3]. The combination of EXE/EVE has doubled the median PFS compared to EXE/placebo at 18 months median follow-up, with good health-related quality of life (HRQoL), and a consistent efficacy in all predefined patient subgroups (i.e., visceral metastases, patients with bone disease, and elderly patients) [4][5][6]. Moreover, the improvement on PFS by the EXE/EVE has been also confirmed into the final analysis performed by Yardley et al [4].…”

Optimizing Quality of Life in Patients with Hormone Receptor-Positive Metastatic Breast Cancer: Treatment Options and Considerations

“…The median TDD for a 5% change from baseline was 8.3 months (95% CI, 7.0-9.7) in the everolimus + exemestane arm compared with 5.8 months (95% CI, 4.2-7.2) in the placebo + exemestane arm. Despite a higher incidence of AEs in the combina- tion arm, QoL analysis concluded that the treatment arm was associated with a longer TDD in global health-related QoL when compared with exemestane alone [77] .…”

“…[77,78] . The validity, reliability, and relevance of these scales for patients with cancer have been clearly demonstrated [78,79] .…”

“…Examples of assessments in these QoL scales include the ability to perform physical activities; need for help with activities of daily living; extent of symptoms such as pain, fatigue, weakness, gastrointestinal issues, sleep disturbances, sexual dysfunction, and degree of emotional and psychological well-being and their impact on QoL [78][79][80] . Findings from select clinical studies that included assessment of patient QoL are summarized in Table 5 [65,77,[81][82][83][84][85][86] .…”

“…In the phase 3 BOLERO 2 study, which compared everolimus plus exemestane with exemestane plus placebo in postmenopausal women with HR-positive MBC that had recurred or progressed on a nonsteroidal AI ( Table 3 ), QoL was measured using the EORTC-QLQ-30 [55,77] . Time to definitive deterioration (TDD) in global health-related QoL was defined as a 5% decrease from baseline with no subsequent increase above this level, based on established criteria for minimally important differences from a patient perspective.…”