Abstract P5-18-01: Extended continuous vs intermittent adjuvant letrozole in postmenopausal women with lymph node-positive, early breast cancer (IBCSG 37-05/BIG 1-07 SOLE): Impact on patient-reported symptoms and quality of life
Authors: Ribi K , Luo W , Colleoni M , Karlsson P , Chirgwin J , Aebi S , Jerusalem G , Neven P , Di Lauro V , Gomez HL , Ruhstaller T , Abdi E , Di Leo A , Müller B , Maibach R , Gelber RD , Goldhirsch A , Coates AS , Regan MM , Bernhard J 
Published: February 2018

Abstract
Background: SOLE efficacy results presented at ASCO 2017 showed that extended intermittent vs continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women who had received 4-6 years of adjuvant endocrine therapy for hormone-receptor positive (HR+), lymph-node positive breast cancer. Previous studies showed that the burden by symptoms related to endocrine therapy can be substantial. Even if symptoms improve during the treatment course, extending treatment implies continuation of symptoms. We compared differences in patient-reported symptoms (PRS) and quality of life (QoL) between extended continuous and intermittent letrozole over the first two years of trial treatment.
Methods: From Nov 2007 to Dec 2010, 956 postmenopausal women who were disease-free following 4-6 years of prior adjuvant endocrine therapy for HR+, node-positive breast cancer were enrolled in the QoL substudy of the randomized phase III trial SOLE at selected centers. Patients receive extended continuous letrozole (2.5 mg daily) for 5 years or intermittent letrozole, taken for the first 9 months of years 1-4, and 12 months in year 5. 955 patients completed the 18-item Breast Cancer Prevention Trial (BCPT) Symptom Scales and further symptom-specific and global QoL indicators at baseline, and at 6, 12, 18 and 24 months after randomization. Differences in change of PRS and QoL from baseline between the two administration schedules were tested at 12 and 24 months for 8 symptom scales, 4 additional symptom and 4 global QoL indicators using mixed models with repeated measures.
Results: Small changes in PRS and QoL scores were observed between baseline and 12 months after randomization, i.e. at the end of the first treatment-free interval in the intermittent arm. These changes showed a consistent pattern of greater worsening for patients receiving continuous compared to patients receiving intermittent letrozole. Patients receiving continuous letrozole reported a significantly greater worsening in vaginal problems (p&lt;.02), musculoskeletal pain (p&lt;.03), sleep disturbance (p&lt;.01), physical wellbeing (p&lt;.01) and mood (p&lt;.03). At 24 months (after 2nd treatment-free interval) patients with intermittent letrozole reported a greater improvement in hot flushes (p&lt;.03) than those with continuous letrozole. Changes in the other outcomes did not significantly differ between arms at 24 months.
Conclusion: Although changes in PRS and QoL were small, there was a consistent pattern favoring the intermittent arm. For several symptoms and global QoL indicators, significantly less worsening was observed with the intermittent administration, mainly during the first year of extended treatment, due to small improvements during the treatment-free interval. Froma QoL perspective, women who suffer from endocrine side-effects in the extended setting may benefit from an intermittent administration.
Citation Format: Ribi K, Luo W, Colleoni M, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Di Lauro V, Gomez HL, Ruhstaller T, Abdi E, Di Leo A, Müller B, Maibach R, Gelber RD, Goldhirsch A, Coates AS, Regan MM, Bernhard J. Extended continuous vs intermittent adjuvant letrozole in postmenopausal women with lymph node-positive, early breast cancer (IBCSG 37-05/BIG 1-07 SOLE): Impact on patient-reported symptoms and quality of life [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-18-01.