338TiP - EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA)

Background

(Neo)adjuvant systemic treatment, with chemotherapy and/or endocrine therapy (ET), substantially reduces the recurrence rates of estrogen receptor positive (ER+) human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer (BC). However, recurrences still occur up to 20 years after diagnosis. Circulating tumor DNA (ctDNA) has emerged as a useful biomarker for surveillance in several solid tumors. ctDNA-based detection of molecular recurrence could allow the start of effective therapies before the clinical evidence of metastases. Elacestrant, a selective ER degrader, approved in the advanced setting of ER+/HER2- ESR1-mutated BC following progression on a CDK4/6-inhibitor, could be used at the time of ctDNA relapse to delay the occurrence of distant metastasis.

Trial design

TREAT ctDNA is an European Organisation for REsearch and Treatment of Cancer (EORTC)-led intergroup international, multicentre, randomised, open label, superiority phase III trial, conducted under the Breast International Group (BIG) umbrella, of adjuvant elacestrant vs standard ET in patients with ER+/HER2- BC and a ctDNA relapse comprising both a screening and a randomised phase. Screening phase: 1960 patients with intermediate to high risk of recurrence stage II or III ER+/HER2- BC on medium to long duration ET will be screened for a ctDNA relapse every 6 months using a personalized, tumor-informed assay (SignateraTM, Natera, Inc.). Randomised phase: 220 ctDNA-positive patients without evidence of recurrence in imaging will be randomised 1:1 between continuing their ET versus receiving elacestrant for 2 years. Participants will undergo intensive follow-up with computed tomography and bone scans, in addition to the standard annual breast imaging for 3 years. The primary endpoint is distant metastasis free survival and secondary endpoints are invasive disease-free survival, relapse-free survival, overall survival, safety and quality of life. Recruitment started in December 2023 in Belgium and is planned to open in 11 more countries in 2024: Cyprus, France, Germany, Greece, Italy, Ireland, the Netherlands, Portugal, Spain, Sweden, and Switzerland.

Clinical trial identification

EU trial number 2022-501453-36-00. NCT05512364.

Editorial acknowledgement

Legal entity responsible for the study

EORTC - European Organization for Research and Treatment of Cancer.

Funding

BERLIN-CHEMIE AG MENARINI from Germany for financial support.

Disclosure

M. Ignatiadis: Financial Interests, Personal, Invited Speaker: Novartis, Daichi, Menarini Group; Financial Interests, Personal, Other, Independent monitoring committee: Seattle Genetics; Financial Interests, Personal, Other, Grants review: Gilead Sciences; Financial Interests, Personal, Other, consultant: Rejuveron Senescence Therapeutics; Financial Interests, Institutional, Other, travel grants: AstraZeneca; Financial Interests, Institutional, Coordinating PI: Pfizer, Roche, Natera, Inivata Inc; Non-Financial Interests, Officer: EORTC. E. Saloustros: Financial Interests, Personal, Advisory Board: Pfizer Hellas, Merck, Sharp & DOHME ΑΦΒΕΕ, Astrazeneca A.E., Gilead Sciences Hellas, PHARMASERVE/LILLY, INTEGRIS Pharma; Financial Interests, Personal, Invited Speaker: GSK, Merck, Sharp & DOHME, ASTRAZENECA A.E.; Financial Interests, Personal and Institutional, Coordinating PI: Merck, Sharp & DOHME ΑΦΒΕΕ, Celcuity, Gilead Sciences; Non-Financial Interests, Member of Board of Directors: Hellenic Society of Medical Oncology; Other, Travel and education: Merck, Sharp & DOHME ΑΦΒΕΕ, Pierre-Fabre Farmaka S.A, Pfizer Hellas. A. Joaquim: Financial Interests, Personal, Advisory Board, February 2022: Novartis, Roche; Financial Interests, Personal, Invited Speaker, March and April 2022: GSK; Financial Interests, Personal, Invited Speaker, May 2022: Merck, MSD; Financial Interests, Institutional, Advisory Board, 2023: EISAI; Financial Interests, Personal, Invited Speaker, March 2022: Gillead, Pfizer; Financial Interests, Personal, Other, Scientific consultant. Until April 2022: Novartis; Financial Interests, Personal, Full or part-time Employment: EORTC. C.M. Kelly: Financial Interests, Personal, Advisory Board: Novartis, Daiichi Sankyp, AstraZeneca; Financial Interests, Personal, Other, Conference attendance/travel expenses: Novartis; Non-Financial Interests, Personal, Other, Steering Committee Member Destiny Breast 11: AstraZeneca. E. Razis: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Servier; Financial Interests, Personal, Funding: Tesaro, Exelixis, AstraZeneca, PPD, MSD; Financial Interests, Personal, Local PI: IQVIA; Non-Financial Interests, Member: ASCO, EANO, SNO, SNOSSA, EUSOMA, BIG; Other, Travel, Accommodations, Expenses: Roche, Pfizer, Karyo, Genesis Pharmaceuticals; Other, Travel to conference support: Servier; Other, Conference attendance support: Gilead, AstraZeneca. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Menarini, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche, AstraZeneca, Menarini, Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2023 and ASCO 2024: Daiichi Sankyo; Financial Interests, Personal, Other, Travel grant to attend SABCS 2023: Roche; Financial Interests, Institutional, Coordinating PI, 2-year research grant paid to my Institution: Gilead; Non-Financial Interests, Leadership Role, Chair of the ESMO Young Oncologists Committee from 01/2023 to 12/2024: ESMO; Non-Financial Interests, Member of Board of Directors, Member of the national council of the Italian Association of Medical Oncology (AIOM): AIOM. T. Foukakis: Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Royalties, Authorship of two chapters in UpToDate: Wolters Kluwer; Financial Interests, Institutional, Coordinating PI, Clinical trial support (research grant and study drug): AstraZeneca; Financial Interests, Institutional, Coordinating PI, Clinical trial support (research grant and study drug): Novartis; Financial Interests, Institutional, Coordinating PI, Discount on the Prosigna PAM50 assay in ARIADNE clinical trial: Veracyte. T. Antoniolli Crestani: Financial Interests, Institutional, Full or part-time Employment, Scientific Advisor: Breast International Group (BIG); Financial Interests, Institutional, Research Grant: AstraZeneca, Roche/Genentech, Novartis, Pfizer, GSK, Sanofi/Aventis. S. Pernas Simon: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca- Daiichi Sankyo, Pierre-Fabre, Pfizer; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Eisai, Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Novartis, Daichii-Sankyo; Non-Financial Interests, Member of Board of Directors: SOLTI. P. Neven: Financial Interests, Institutional, Advisory Role, last 12 months: Pfizer, Novartis, Eli Lilly, Roche, AstraZeneca; Financial Interests, Institutional, Advisory Board, last 12 months: AstraZeneca, Pfizer, Novartis, Eli Lilly, Roche, Medscape, Gilead, Menarini. T. Meyskens: Financial Interests, Personal, Other, Consultancy: Astellas; Financial Interests, Personal, Advisory Board: Merck KGaA. F.C. Bidard: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Novartis, AstraZeneca, GE Healthcare, SAGA Diagnostics, Daiichi Sankyo, Gilead, Inatherys; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Pfizer, Merck KGaA, Roche; Financial Interests, Institutional, Funding: Prolynx, Saga Diagnostics, Merck KGaA; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Lilly, Pfizer; Financial Interests, Personal and Institutional, Steering Committee Member: Lilly. W. Janni: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead; Financial Interests, Personal, Full or part-time Employment: Universitätsklinikum Ulm; Financial Interests, Institutional, Coordinating PI: Novartis, GSK, Sanofi, Amgen, Roche, Lilly; Non-Financial Interests, Leadership Role: Chair of AGO Breast Council. All other authors have declared no conflicts of interest.