SOLE (Study of Letrozole Extension): A phase III randomized clinical trial of continuous vs intermittent letrozole in postmenopausal women who have received 4-6 years of adjuvant endocrine therapy for lymph node-positive, early breast cancer (BC)
| Autor: | Michael Gnant, Katsumasa Kuroi, Marco Colleoni, Patrick Neven, Alan S. Coates, Meredith M. Regan, Per Karlsson, Sibylle Loibl, Alastair M. Thompson, Marie-Pascale Graas, Weixiu Luo, Claus Kamby, Edda Simoncini, Aron Goldhirsch, Stefan Aebi, Erika Hitre, Manuela Rabaglio-Poretti, Guy Jerusalem, Joaquín Gavilá, J. Chirgwin |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Randomization medicine.medical_treatment Malignancy law.invention 03 medical and health sciences 0302 clinical medicine Breast cancer Randomized controlled trial law Internal medicine medicine Adjuvant therapy Clinical endpoint Gynecology business.industry Letrozole medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis business Adjuvant medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 35:503-503 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 503 Background: In animal models of hormone receptor positive (HR+) breast cancer, acquired resistance to continued letrozole was shown to be reversed by estrogen-induced apoptosis. Sensitization to reintroduction of estrogen withdrawal by letrozole was hypothesized to improve treatment outcome. SOLE tested the hypothesis that 3 mos treatment-free intervals during extended adjuvant therapy will improve disease-free survival (DFS). Methods: SOLE enrolled 4884 postmenopausal women with HR+ lymph node-positive BC who had completed 4-6 yrs of adjuvant endocrine therapy (19% SERM, 43% AI, 38% both; stratification factor). Pts were randomly assigned to an additional 5 yrs continuous letrozole (2.5 mg daily; n = 2441) vs 5 yrs intermittent letrozole (taken for the first 9 mos of yrs 1-4, and 12 mos in yr 5; n = 2443). The primary endpoint was DFS (randomization until invasive local, regional, distant recurrence or contralateral BC; 2nd malignancy; death). Final analysis was at 665 DFS events, after 2 interim analyses. SOLE required 4800 pts for 80% power to detect a 20% DFS hazard reduction with 2-sided α = 0.05 using a stratified log rank test. Analysis is by intention-to-treat. Results: At 60 mos median follow-up, 5 yr DFS from randomization was 85.8% vs 87.5% for patients assigned intermittent vs continuous letrozole (HR = 1.08; 95% CI 0.93-1.26; P = 0.31). Similar outcome was observed for breast cancer-free interval (HR = 0.98; 95% CI 0.81-1.19), distant recurrence-free interval (HR = 0.88; 95% CI 0.71-1.09), and overall survival (HR = 0.85; 95% CI 0.68-1.07). AEs of grade > 3 were reported for 43.5% vs 41.6% of pts assigned intermittent vs continuous letrozole. Overall 24% pts discontinued letrozole early in both groups. Conclusions: Among postmenopausal women with HR+ BC, extended intermittent letrozole did not improve DFS vs continuous letrozole. The similar observed outcomes and incidence of AEs provides clinically relevant information on the intermittent administration of extended letrozole for patients who could benefit from temporary treatment breaks. Clinical trial information: NCT00553410. |
| Databáze: | OpenAIRE |
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