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- Jerusalem, G, et al.
(författare)
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Continuous versus intermittent extended adjuvant letrozole for breast cancer: Final results of randomized phase 3 SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.
- 2021
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1256-1266
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Tidskriftsartikel (refereegranskat)abstract
- Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy. In animal models, resistance was reversed with restoration of circulating estrogen level during interruption of letrozole treatment. This phase 3 randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen sub-study (SOLE-EST) analyzed the level of estrogen during the interruption of treatment.SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant endocrine therapy. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all year 5).Intention-to-treat population included 4851 women in SOLE (n=2425 in intermittent and n=2426 in continuous letrozole groups) and 103 women in SOLE-EST (n=78 in intermittent and n=25 in continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival was 81.4% in intermittent group and 81.5% in continuous group (hazard ratio: 1.03, 95%CI: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment.Extended adjuvant endocrine therapy by intermittent administration of letrozole did not improve disease-free survival compared to continuous use despite the recovery of circulating estrogen level. The similar disease-free survival coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.
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| 2. |
- Ribi, Karin, et al.
(författare)
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Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.
- 2019
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 120, s. 959-967
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Tidskriftsartikel (refereegranskat)abstract
- In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients' quality of life (QoL).In the SOLE QoL sub-study, 956 patients completed the Breast Cancer Prevention Trial (BCPT) symptom and further QoL scales up to 24 months after randomisation. Differences in change of QoL from baseline between the two administration schedules were tested at 12 and 24 months using repeated measures mixed-models. The primary outcome was change in hot flushes at 12 months.There was no difference in hot flushes at 12 months between the two schedules, but patients receiving intermittent letrozole reported significantly more improvement at 24 months. They also indicated less worsening in vaginal problems, musculoskeletal pain, sleep disturbance, physical well-being and mood at 12 months. Overall, 25-30% of patients reported a clinically relevant worsening in key symptoms and global QoL.Less symptom worsening was observed during the first year of extended treatment with the intermittent administration. For women experiencing an increased symptom burden of extended adjuvant endocrine therapy, an intermittent administration is a safe alternative.Clinical trial information: NCT00651456.
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