Specific adverse events predict survival benefit in patients treated with
tamoxifen or aromatase inhibitors: an international tamoxifen exemestane adjuvant
multinational trial analysis.
Author(s): Fontein DB(1), Seynaeve C, Hadji P, Hille ET, van de Water W, Putter H,
Kranenbarg EM, Hasenburg A, Paridaens RJ, Vannetzel JM, Markopoulos C, Hozumi Y,
Bartlett JM, Jones SE, Rea DW, Nortier JW, van de Velde CJ.
Affiliation(s): Author information:
(1)Leiden University Medical Center, Leiden, The Netherlands.
Publication date & source: 2013, J Clin Oncol. , 31(18):2257-64
PURPOSE: Specific adverse events (AEs) associated with endocrine therapy and
related to depletion or blocking of circulating estrogens may be related to
treatment efficacy. We investigated the relationship between survival outcomes
and specific AEs including vasomotor symptoms (VMSs), musculoskeletal adverse
events (MSAEs), and vulvovaginal symptoms (VVSs) in postmenopausal patients with
breast cancer participating in the international Tamoxifen Exemestane Adjuvant
Multinational (TEAM) trial.
PATIENTS AND METHODS: Primary efficacy end points were disease-free survival
(DFS), overall survival (OS), and distant metastases (DM). VMSs, MSAEs, and VVSs
arising in the first year of endocrine treatment were considered. Patients who
did not start or who discontinued their allocated therapy and/or had an event
(recurrence/death) within 1 year after randomization were excluded. Landmark
analyses and time-dependent multivariate Cox proportional hazards models assessed
survival differences up to 5 years from the start of treatment.
RESULTS: A total of 9,325 patients were included. Patients with specific AEs (v
nonspecific or no AEs) had better DFS and OS (multivariate hazard ratio [HR] for
DFS: VMSs, 0.731 [95% CI, 0.618 to 0.866]; MSAEs, 0.826 [95% CI, 0.694 to 0.982];
VVSs, 0.769 [95% CI, 0.585 to 1.01]; multivariate HR for OS: VMSs, 0.583 [95% CI,
0.424 to 0.803]; MSAEs, 0.811 [95% CI, 0.654 to 1.005]; VVSs, 0.570 [95% CI,
0.391 to 0.831]) and fewer DM (VMSs, 0.813 [95% CI, 0.664 to 0.996]; MSAEs, 0.749
[95% CI, 0.601 to 0.934]; VVSs, 0.687 [95% CI, 0.436 to 1.085]) than patients not
reporting these symptoms. Increasing numbers of specific AEs were also associated
with better survival outcomes. Outcomes were unrelated to treatment allocation.
CONCLUSION: Certain specific AEs are associated with superior survival outcomes
and may therefore be useful in predicting treatment responses in patients with
breast cancer treated with endocrine therapy.
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