| 1. |
- Aapro, Matti, et al.
(author)
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The MAGIC survey in hormone receptor positive (HR+), HER2-negative (HER2−) breast cancer: When might multigene assays be of value?
- 2017
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In: Breast. - : Elsevier BV. - 0960-9776 .- 1532-3080. ; 33, s. 191-199
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Journal article (peer-reviewed)abstract
- © 2017 Background A modest proportion of patients with early stage hormone receptor-positive (HR+), HER2-negative (HER2−) breast cancer benefit from adjuvant chemotherapy. Traditionally, treatment recommendations are based on clinical/pathologic criteria that are not predictive of chemotherapy benefit. Multigene assays provide prognostic and predictive information that can help to make more informed treatment decisions. The MAGIC survey evaluated international differences in treatment recommendations, how traditional parameters are used for making treatment choices, and for which patients treating physicians feel most uncertain about their decisions. Methods The MAGIC survey captured respondents' demographics, practice patterns, relevance of traditional parameters for treatment decisions, and use of or interest in using multigene assays. Using this information, a predictive model was created to simulate treatment recommendations for 672 patient profiles. Results The survey was completed by 911 respondents (879 clinicians, 32 pathologists) from 52 countries. Chemo-endocrine therapy was recommended more often than endocrine therapy alone, but there was substantial heterogeneity in treatment recommendations in 52% of the patient profiles; approximately every fourth physician provided a different treatment recommendation. The majority of physicians indicated they wanted to use multigene assays clinically. Lack of reimbursement/availability were the main reasons for non-usage. Conclusions The survey reveals substantial heterogeneity in treatment recommendations. Physicians have uncertainty in treatment recommendations in a high proportion of patients with intermediate risk features using traditional parameters. In HR+, HER2− patients with early disease the findings highlight the need for additional markers that are both prognostic and predictive of chemotherapy benefit that may support more-informed treatment decisions.
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| 2. |
- Colleoni, Marco, et al.
(author)
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Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.
- 2018
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In: The Lancet. Oncology. - : Elsevier. - 1474-5488 .- 1470-2045. ; 19:1, s. 127-138
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Journal article (peer-reviewed)abstract
- In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women.We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing.Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85·8% (95% CI 84·2-87·2) in the intermittent letrozole group compared with 87·5% (86·0-88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93-1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group).In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them.Novartis and the International Breast Cancer Study Group.
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| 4. |
- Ribi, Karin, et al.
(author)
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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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In: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 120, s. 959-967
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Journal article (peer-reviewed)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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