OT2-02-01: The SOLE Trial: International Breast Cancer Study Group (IBCSG 35–07) and Breast International Group (BIG 1–07) Study of Letrozole Extension.
Authors: Colleoni M 
Published: June 2012

Abstract
Background The SOLE trial tests the hypothesis that treatment-free intervals during the course of five years of extended adjuvant letrozole will improve disease-free survival (DFS). The hypothesis is based on the observation in animal models that intermittent letrozole withdrawal will permit some estrogenic stimulation which makes residual resistant disease susceptible to letrozole reintroduction.
Trial Design Randomized, Phase III trial comparing 5 years of continuous letrozole vs. 5 years of intermittent letrozole. The intermittent group receives letrozole daily for the first 9 months (followed by a 3-month gap) years 1–4, and 12 months year 5. Stratification factors are institution and prior endocrine therapy (SERM, AI or both).
Major Eligibility Criteria
-Postmenopausal
-Disease-free
-Received 4–6 years of prior adjuvant endocrine therapy (SERM and/or AI)
-Randomized within 12 months of last dose of prior endocrine therapy
-Endocrine-responsive breast cancer at diagnosis
-Node-positive breast cancer at diagnosis
Specific Aim
To compare continuous and intermittent letrozole given for a five year period for postmenopausal women who are disease-free following 4–6 years of prior adjuvant endocrine therapy with SERM(s) and/or AI(s) for endocrine-responsive node-positive operable breast cancer. Statistical Methods
The primary analysis will be undertaken with the intention-to-treat population of all randomized patients. The primary endpoint DFS will be compared between treatment arms using a two-sided stratified logrank test with an overall experiment-wise alpha level equal to at most 0.05.
For the eligible population of patients with node positive disease at initial diagnosis, we assume 90% of patients who receive continuous extended letrozole will be alive and disease-free at 4 years from randomization (based on results of MA.17). The sample size was determined to provide 80% power to detect a 20% reduction in the risk of an event defining DFS associated with intermittent letrozole compared with continuous letrozole (hazard ratio = 0.80; increase in 4-year DFS from 90% to 91.917%) using a two-sided 0.05 level test of significance.
Present and Target Accrual
Target: 4800; Present: 2655 (June 1, 2011)
Related Research
The SOLE-EST Substudy focuses on the changes in estrogen levels that occur on letrozole and during the three month treatment gap without letrozole; and relationships between changes in patient-reported musculoskeletal symptoms, grip strength and QL. The target accrual goal is 100 patients (75 intermittent and 25 continuous).
The SOLE Quality of Life Substudycompares differences in patient-reported symptoms and QL between continuous letrozole for 5 years and intermittent letrozole over a 2-year period. The target accrual goal is 834 patients.
Central Pathology Review for all patients of histology, grade, ER, PgR, HER2, and Ki-67 is ongoing.
Contact Information
The SOLE trial is a worldwide collaboration among cooperative groups and large institutions primarily through the Breast International Group (BIG).
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-02-01.