Abstract 263TiP
Background
Current evidence from both randomized trials and real-world evidence studies suggests that older patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer derive clinical benefit from the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy. However, a higher risk for adverse events due to CDK4/6 inhibitors among older patients is evident, leading to a trend of initiating CDK4/6 inhibitors at a lower dose in clinical practice, though without evidence. The aim of the present randomized trial is to investigate whether lower initial dose of CDK4/6 inhibitors combined with endocrine therapy is comparable to full dose in older patients with advanced HR+/HER2-breast cancer that are assessed as vulnerable/frail based on comprehensive geriatric assessment (CGA).
Trial design
We designed a multi-national, open-label, pragmatic randomized controlled trial with non-inferiority approach. Patients ≥70 years old with advanced HR+/HER2- breast cancer with no curative intention, no prior treatment in an advanced setting, and suitable to receive a combination of CDK4/6 inhibitors plus endocrine therapy according to treating physician, are eligible for study inclusion. After informed consent, included patients fill out a self-administered CGA tool and categorized accordingly to fit, vulnerable, or frail, depending on the number of impaired CGA domains. Fit patients receive full dose of CDK4/6 inhibitors and endocrine therapy whereas vulnerable/frail patients are randomized to either -1 level lower CDK4/6 inhibitor dose or full dose and endocrine therapy. The primary endpoint is time to treatment failure whereas secondary endpoints include overall treatment utility, progression-free survival, overall survival, time to chemotherapy initiation, toxicity, quality-of-life, time to quality-of-life deterioration and cost-effectiveness. In total, 495 patients are planned to be included to allow 346 vulnerable/frail patients to be randomized. Enrolment: The trial is open for recruitment since February 2024 with a recruitment period of 30 months.
Clinical trial identification
NCT06044623.
Legal entity responsible for the study
Region Örebro County.
Funding
This trial has received funding from the European Union’s Horizon Europe research and innovation program under grant agreement No 101104589.
Disclosure
A. Valachis: Financial Interests, Institutional, Research Grant, Research Grant for a research project on Molecular profiling of triple negative breast cancer: Roche; Financial Interests, Institutional, Invited Speaker, PRODAT trial: Novartis; Financial Interests, Institutional, Invited Speaker, CHECKMATE-401 trial: Bristol-Myers-Squibb; Financial Interests, Institutional, Invited Speaker, CHECKMATE-76K trial: Bristol-Myers-Squibb; Financial Interests, Institutional, Invited Speaker, TELEPIK trial: Novartis; Financial Interests, Institutional, Invited Speaker, DESTINY-Breast09 trial: AstraZeneca. L. Biganzoli: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, Gilead, Sanofi, Seattle Genetics, Exact Sciences, Amgen, Boehringer-Ingelheim, Pierre Fabre, Menarini; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Roche; Financial Interests, Institutional, Research Grant: Celgene, Genomic Health, Novartis; Non-Financial Interests, Member of Board of Directors: SIOG. P. Karihtala: Financial Interests, Institutional, Principal Investigator: Lilly, Novartis, Pfizer; Financial Interests, Institutional, Advisory Board: Lilly, Novartis, Pfizer. P.A. Kosmidis: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Registration In Congress: Pfizer; Financial Interests, Personal, Other, Registration To Congress: Sanofi; Financial Interests, Personal, Ownership Interest: Careacross Digital Health Company. H. Linardou: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Merck, Takeda, Bristol Myers Squibb, Lilly, Pfizer, GSK; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, Bristol Myers Squibb, Pfizer, Amgen, Novartis; Financial Interests, Personal, Stocks/Shares: BioPath Innovations S.A.; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squibb, Boehringer Ingelheim, Roche, AbbVie, Lilly, Novartis, AstraZeneca, Amgen, PPD, Parexel ILR, Qualitis, Health Data Specialist; Financial Interests, Institutional, Invited Speaker: GSK; Non-Financial Interests, Principal Investigator: Hellenic Cooperative Oncology Group; Non-Financial Interests, Leadership Role, Elected Chair of the Scientific Committee: Hellenic Cooperative Oncology Group; Non-Financial Interests, Member of Board of Directors: Women 4 Oncology - Hellas, Fairlife Lung Cancer Care, Hellenic Cooperative Oncology Group, Hellenic Foundation for Cancer Research; Non-Financial Interests, Leadership Role, Legal Representattive: Women 4 Oncology- Hellas. I. Meattini: Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Gilead, Seagen, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Expert Testimony: Accuray. M. Munoz: Financial Interests, Personal, Expert Testimony: Roche, Novartis; Financial Interests, Personal, Other, International conference travel grants: Roche, Pfizer, Lilly, Gilead; Financial Interests, Personal, Advisory Board: Pierre Fabre, Seagen, AstraZeneca. A. Psyrri: Financial Interests, Personal, Invited Speaker: MSD, Merck Serono, EPICS; Financial Interests, Personal, Advisory Board: Pfizer, Sanofi, MSD, AstraZeneca, BMS, LEO, Rakuten, eTheRNA immunotherapies, Merck Serono, Seagen, Merus; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Iovance, Pfizer, Pfizer, Roche, GSK, Genesis, Incyte, Amgen, Debiopharm, MSD, Janssen, Lilly, Regeneron, Sanofi, BI, Roche, Peregrine, Oncolytics Biotech; Financial Interests, Invited Speaker: AstraZeneca, Kura Oncology; Financial Interests, Institutional, Invited Speaker: Kura OncologY, Novartis, Replimmune; Financial Interests, Personal and Institutional, Funding: Kura Oncology, BMS, Roche, DEMO, Amgen, BI, Genesis, BMS, Pfizer, Oncolytics Biotech; Financial Interests, Institutional, Funding: Merck Serono, Pfizer; Financial Interests, Personal, Other, Educational activity: MEDSCAPE, PrimeOncology; Non-Financial Interests, Project Lead, Medical Education with honoraria: MEDSCAPE. T. Kosmidis: Financial Interests, Personal, Ownership Interest: CareAcross Ltd. All other authors have declared no conflicts of interest.