Adjuvant Endocrine Therapy (AET) is the cornerstone treatment of localized hormone-receptor-positive (HR+) breast cancer, with demonstrated benefits on overall survival (30-40% relative decrease in mortality) but also on the risk of local and contralateral relapse (43-50% relative decrease). While the relative benefit of 5 years of ET is identical for small tumors as compared to larger ones, the absolute benefit is much lower, and the risk-benefit ratio becomes questionable given the frequent and impactful side effects of ET which are associated with non-adherence. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. Five years appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among rather high-risk patients. However, shorter treatments of 2-3 years were already associated with substantial benefits. The purpose of this study is to demonstrate that AET limited to 2 years of aromatase inhibitor (AI) in postmenopausal women at very low risk of recurrence as determined with a MammaPrint/BluePrint Ultra Low Risk test result can ensure very high survival without metastatic relapse and allows a reduction of side effects and a better quality of life.
LESS is a prospective, national, multicenter, single-arm, interventional, non-threshold crossing phase II study evaluating a therapeutic de-escalation that limits adjuvant ET to 2 years of AI. Approximately 696 post-menopausal patients with an invasive unilateral, HR+, HER2-negative, without indication of adjuvant chemotherapy and genomically-assessed MammaPrint/BluePrint Ultra Low risk luminal A breast cancer tumors, will be enrolled. LESS will include 2 sub cohorts: the majority of patients with Grade 2, pT1c-2, pN0/N1mic tumors, and up to 80 patients ≥65 years with Grade 1, pT1, pN0 and Ki67 ⩽ 10% tumors. The primary endpoint is distant metastasis free survival defined as the time from date of registration to date of 1st event of distant recurrence, death, or 2d primary non-breast invasive cancer. The 1st patient was included in Oct 2022, initiating the 2-year inclusion period.
NCT05297617.
Unicancer.
Agendia.
E. Deluche: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, FRESENIUS-KABI, Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Other, scientific events: Lilly, GSK; Financial Interests, Personal, Other, funding for conference travel: AstraZeneca-Daiichi, Roche, AMGEN. S. Michiels: Financial Interests, Personal, Other, Statistical advice: Roche; Financial Interests, Personal, Other, DSMB member: Sensorion, Servier, Biophytis, Yuhan, IQVIA, Kedrion. C. Bailleux: Other, Travel, accommodations, expenses: AstraZeneca; Financial Interests, Advisory Role: Seagen, Novartis, AstraZeneca. T. Bachelot: Financial Interests, Personal, Advisory Board: Roche, Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca. I.V. Vaz Luis: Financial Interests, Institutional, Invited Speaker: Amgen, Pfizer/Edimark, Pfizer/Edimark, AstraZeneca; Financial Interests, Institutional, Advisory Board, Consulting/ AB: Novartis; Financial Interests, Institutional, Expert Testimony: Sandoz; Financial Interests, Institutional, Funding: Resilience; Non-Financial Interests, Member, Member of WG: ASCO. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Financial Interests, Institutional, Other, advisory board: Guardant Health; Financial Interests, Institutional, Other, Advisory board: MEDIMMUNE, Gilead, Relay therapeutics; Other, Founder: Pegacsy. All other authors have declared no conflicts of interest.