Health-related quality of life and disease symptoms in postmenopausal women with HR⁺, HER2⁻ advanced breast cancer treated with everolimus plus exemestane versus exemestane monotherapy

Abstract

Objective:

Everolimus (EVE)+exemestane (EXE; n = 485) more than doubled median progression-free survival versus placebo (PBO) + EXE (n = 239), with a manageable safety profile and no deterioration in health-related quality-of-life (HRQOL) in patients with hormone-receptor-positive (HR⁺) advanced breast cancer (ABC) who recurred or progressed on/after nonsteroidal aromatase inhibitor (NSAI) therapy. To further evaluate EVE + EXE impact on disease burden, we conducted additional post-hoc analyses of patient-reported HRQOL.

Research design and methods:

HRQOL was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and every 6 weeks thereafter until treatment discontinuation because of disease progression, toxicity, or consent withdrawal. Endpoints included the QLQ-C30 Global Health Status (QL2) scale, the QLQ-BR23 breast symptom (BRBS), and arm symptom (BRAS) scales. Between-group differences in change from baseline were assessed using linear mixed models with selected covariates. Sensitivity analysis using pattern-mixture models determined the effect of study discontinuation on/before week 24. Treatment arms were compared using differences of least squares mean (LSM) changes from baseline and 95% confidence intervals (CIs) at each timepoint and overall.

Clinical trial registration:

Clinicaltrials.gov: NCT00863655.

Main outcome measures:

Progression-free survival, survival, response rate, safety, and HRQOL.

Results:

Linear mixed models (primary model) demonstrated no statistically significant overall difference between EVE + EXE and PBO + EXE for QL2 (LSM difference = −1.91; 95% CI = −4.61, 0.78), BRBS (LSM difference = −0.18; 95% CI = −1.98, 1.62), or BRAS (LSM difference = −0.42; 95% CI = −2.94, 2.10). Based on pattern-mixture models, patients who dropped out early had worse QL2 decline on both treatments. In the expanded pattern-mixture model, EVE + EXE-treated patients who did not drop out early had stable BRBS and BRAS relative to PBO + EXE.

Key limitations:

HRQOL data were not collected after disease progression.

Conclusions:

These analyses confirm that EVE + EXE provides clinical benefit without adversely impacting HRQOL in patients with HR⁺ ABC who recurred/progressed on prior NSAIs versus endocrine therapy alone.

Keywords::

• Advanced breast cancer
• Everolimus
• Exemestane
• Health-related quality of life
• Hormone receptor positive

Transparency

Declaration of funding

This work was supported by Novartis Pharmaceuticals. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals.

M.C., M.G., P.N., H.S.R., M.P., J.B., T.S., and H.A.B. were involved in the conception and design of the manuscript. M.C., J.T.B., M.G., T.B., H.S.R., D.Y.C.H., J.B., A.C., and H.A.B. were involved in the collection and assembly of data. M.C., M.G., K.I.P., L.P., H.S.R., G.N.H., M.N., J.B., S.N., J.H., L.B., R.Z., J.Z., and H.A.B. were involved in data analysis and interpretation. M.C., J.T.B., M.G., P.N., K.I.P., L.P., H.S.R., G.N.H., M.N., D.Y.C.H., J.B., S.N., J.H., L.B., R.Z., J.Z., A.C., T.S., and H.A.B. were involved in writing the manuscript. M.C., J.T.B., M.G., P.N., K.I.P., T.B., L.P., H.S.R., M.P., G.N.H., M.N., D.Y.C.H., J.B., S.N., J.H., L.B., R.Z., J.Z., A.C., T.S., and H.A.B. provided final approval of the manuscript.

Declaration of financial/other relationships

M.C. has received research funding from Novartis and has acted as a consultant or advisor for Novartis and Servier. J.T.B. has received institutional research funds. M.G. has received research funding from Sanofi-Aventis, Novartis, Roche, and Pfizer, and has participated in a speaker’s bureau for Amgen, Novartis, Pfizer, Bayer, Sandoz, GlaxoSmithKline and AstraZeneca. K.I.P. has received research funding and acted as a consultant/advisor for Novartis. T.B. has received research funding from and acted as a consultant/advisor for Roche and Novartis, and has participated in a speaker’s bureau for Novartis. L.P. has received sponsorship, research funding, and acted as a consultant/advisor for Novartis. H.S.R. has received research funding from Novartis. M.P. has received research funding from Pfizer, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Roche-Genentech, and Sanofi-Aventis; has acted as a consultant/advisor for Sanofi-Aventis, Amgen, Roche-Genentech, Bayer, AstraZeneca, Pfizer, Verastem, MSD, Synthon, Invivis, Astellas, and Symphogen; has received honoraria from Bayer, Roche-Genentech, Amgen, Sanofi-Aventis, AstraZeneca, and Novartis; and is a board member of PharmaMar. G.N.H. has received institutional research funding from Novartis, and has acted as a consultant/advisor for Allergan, Galena, Genentech, AstraZeneca, Novartis and Sanofi-Aventis. D.Y.C.H. has acted as a consultant/advisor for Bayer, Pfizer, and Novartis. J.B. has acted as a consultant/advisor for Novartis, Roche Genentech, and Aragon. S.N. has received research funding from Novartis and Pfizer, and has acted as a consultant for Novartis. L.B. has acted as a consultant/advisor for Novartis. J.Z., A.C., T.T., and T.S. have disclosed that they are Novartis employees and stockholders. P.N., M.N., A.K., J.H., R.Z. and H.A.B. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have received honoraria for their review work, but have no other relevant financial or other relationships to disclose.

Acknowledgments

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. The authors thank Marithea Goberville PhD and Jerome F. Sah PhD, ProEd Communications Inc., for medical editorial assistance with this manuscript.

Previous publication: Portions of the data were presented at ESMO 2012 (abstract 334P).