Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial

Abstract

Purpose: Treatment-emergent symptoms with adjuvant tamoxifen and aromatase inhibitors (AIs) have been associated with superior recurrence-free survival (RFS). We hypothesized that MA.27 anastrozole- or exemestane-treated patients with new or worsening vasomotor and/or joint symptoms would have improved RFS.

Patients and methods: MA.27 randomly assigned 7,576 postmenopausal women with breast cancer to 5 years of anastrozole or exemestane. Patient-reported symptoms were collected using the Common Terminology Criteria for Adverse Events version 3.0 at protocol-specified baseline and 6- and 12-month clinical visits. Symptoms were considered present with either vasomotor and/or joint complaints. Associations between symptoms and baseline patient characteristics were examined with χ(2) and Fisher's exact tests. Subsequent effects of new or worsening symptoms on RFS were examined with landmark analyses and stratified univariable and multivariable Cox models. We examined the effects of 3-month symptoms arising from unplanned clinic visits as a result of severe toxicity.

Results: Patients were assessable if eligible for the MA.27 trial, received some trial therapy, and had no disease recurrence at the end of a symptom assessment period; 96% of patients (n = 7,306 patients) were included at 6 months, and 96% (n = 7,246) were included at 12 months. Thirty-four percent of patients had baseline symptoms. For patients without baseline symptoms, 25% and 52% had new symptoms by 6 and 12 months, respectively. Neither treatment-emergent nor baseline symptoms significantly impacted RFS (P > .10) in patients with or without baseline symptoms.

Conclusion: In MA.27, anastrozole or exemestane treatment-emergent symptoms were not associated with improved RFS. Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms.

Trial registration: ClinicalTrials.gov NCT00066573.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2014 by American Society of Clinical Oncology.

Figures

Fig 1.

CONSORT diagram for NCIC Clinical Trials Group MA.27. Group 1 patients are a subgroup of group 3; group 2 patients are a subgroup of group 1; and group 3 patients are all patients assessed for musculoskeletal (MSK) and vasomotor (VM) symptoms.

Fig 2.

Time to treatment discontinuation in women without new or worsening symptoms by 12 months. HR, hazard ratio.

Fig 3.

Time to treatment discontinuation in women with new or worsening symptoms by 12 months. HR, hazard ratio.

Fig 4.

Recurrence-free survival of group 1 patients without baseline vasomotor (vaso) or grade 3 or 4 joint symptoms who developed vasomotor or grade 3 or 4 joint symptoms at 6 months. HR, hazard ratio.

Fig 5.

Recurrence-free survival of group 1 patients without baseline vasomotor (vaso) or grade 3 or 4 joint symptoms who developed vasomotor or grade 3 or 4 joint symptoms at 12 months. HR, hazard ratio.

Fig A1.

Recurrence-free survival of group 1 patients without baseline vasomotor (vaso) or grade 3 or 4 joint symptoms who developed vasomotor or grade 3 or 4 joint symptoms at 3 months. HR, hazard ratio.

Fig A2.

Recurrence-free survival of group 3 patients with new or worsening vasomotor (vaso) or joint symptoms at 3 months. HR, hazard ratio.

Fig A3.

Recurrence-free survival of group 3 patients (women) with new or worsening vasomotor (vaso) or joint symptoms at 6 months. HR, hazard ratio.

Fig A4.

Recurrence-free survival of group 3 patients (women) with new or worsening vasomotor (vaso) or joint symptoms at 12 months. HR, hazard ratio.