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Analysis of BOLERO-2 Trial Shows No Negative Effect on Health-Related Quality of Life

Everolimus plus exemestane improves progression-free survival, while maintaining health-related quality of life, in women with hormone receptor-positive, metastatic breast cancer

September 17, 2013

Written By Nicole Katze, MA, Writer and Editorial Coordinator
Reviewed By Richard A. Michaelson, MD

Postmenopausal women with metastatic, hormone receptor-positive breast cancer who are treated with everolimus (Afinitor) plus exemestane (Aromasin) experience delays in cancer progression while maintaining the same quality of life they would have if treated with exemestane alone, a secondary analysis of the BOLERO-2 trial found.

Early findings from the phase III BOLERO-2 trial showed that the combination of everolimus plus exemestane significantly improved progression-free survival, the time from the start of treatment to disease growth or death from any cause, in women who had breast cancer progress after being treated with the aromatase inhibitors letrozole or anastrozole. These findings led to FDA approval of everolimus for treating women with HER2-negative, metastatic breast cancer in 2012.

Background 

BOLERO-2 investigators tested whether everolimus, an mTOR inhibitor, would make hormonal therapies like exemestane more effective, by comparing progression-free survival in women treated with everolimus plus exemestane versus exemestane plus a placebo (an inactive substance). mTOR inhibitors work by slowing or stopping the function of mTOR protein kinases, enzymes that help encourage cell growth.

Because a woman diagnosed with metastatic breast cancer remains in treatment throughout her life, a treatment’s impact on her health-related quality of life (HRQOL) is important for assessing whether it is the best therapy for her. HRQOL helps define how your mental and physical health make your life more positive or negative, and takes into account how both the disease symptoms and the treatment side effects impact you overall. A medicine that causes more negative health effects, like pain or fatigue, may lead to a decrease in HRQOL if it does not also control the symptoms of the disease.

Comparing HRQOL in women treated with everolimus plus exemestane versus exemestane plus a placebo was a secondary goal of BOLERO-2. The researchers conducting this secondary analysis reported on that data.

Design 

Participants in the BOLERO-2 trial filled out the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-30) when they joined the study, and then every 6 weeks until they left the study for any reason, or the study ended. The EORTC QLQ-30 is a 30-item survey used in clinical trials to estimate better or worse health-related quality of life.

Based on these surveys, the researchers explored the time to definitive deterioration (TDD) in quality of life scores. TDD is the length of time it took a woman to report a 5 percent drop in HRQOL from her baseline score. To strengthen the results, the investigators reassessed TDD using another quality of life scale known as minimal important differences (MID).

Participants were postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed after treatment with aromatase inhibitors. 

Results 

At enrollment, 455 women in the everolimus treatment group and 225 women in the placebo group completed the questionnaire. By week 48 of the trial, nearly 80 percent of the women still completed surveys; after week 48 participation dropped. Results are based on data collected from the baseline enrollment questionnaire through week 48 only.

Overall, the researchers found that the combination of everolimus and exemestane does not have a negative effect on HRQOL when compared with treatment with a placebo and exemestane.

The data also showed:

  • At enrollment, both groups of women had similar quality of life scores.
  • When TDD was defined as a 5 percent decrease in HRQOL from baseline, TDD was 8.3 months with everolimus plus exemestane and 5.8 months with exemestane plus placebo; TDD remained longer when defined by the MID scale.
  • TDD improved in the everolimus group despite more reports of major side effects than in the placebo group. This result maybe because TDD controlled disease-related symptoms better.

Limitations

This study was limited by the high number of missing questionnaires over the course of the trial. The investigators believe everolimus plus exemestane may be more beneficial than these findings show.

What This Means for You

If you are a woman with hormone receptor-positive, HER2-negative, metastatic breast cancer, this study may ease any worries you may have had about the impact of side effects on your quality of life while taking everolimus plus exemestane. Though more women on the combination treatment experienced serious side effects than on exemestane alone, the combination lengthens progression-free survival without causing quality of life, as measured in this study, to worsen.

You and your healthcare team will talk regularly about what treatments are available to you as a woman with metastatic disease. If you already had the cancer progress on letrozole or anastrozole and are interested in treatment with everolimus plus exemestane, talk with your doctor about these findings or for more information.

Burris, III, H, Lebrun, F, Rugo, H, et al. Health-related quality of life in patients with advanced breast cancer treated with everolimus plus exemestane versus placebo plus exemestane in the phase III, randomized, controlled, BOLERO-2 trial. Cancer; (2013) 199 (10):1908-1915.

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