Everolimus or ribociclib in patients with HER2-negative, hormone-receptor positive metastatic breast cancer and circulating tumor cells: Results from DETECT IVa

BackgroundDETECT-IVa is a single-arm, open-label phase II study for postmenopausal patients with HER2-negative, hormone-receptor (HR) positive metastatic breast cancer (MBC) and HER2-negative circulating tumor cells (CTCs) in the 1st – 3rd metastatic treatment line. The main aim of the study was to assess the suitability of CTC clearance to provide prognostic and/or predictive information regarding treatment efficacy.MethodsDETECT IVa (patient recruitment from 2014 – 2020) comprised two subsequent patient cohorts receiving endocrine therapy combined with the mTOR inhibitor everolimus (until 2018, n = 90) and the CDK 4/6 inhibitor ribociclib (after EMA approval in 2018, n=26). Here we present data on progression-free survival (PFS) and overall survival (OS) for the full patient cohort (n = 116) as well as data on the association between CTC clearance rate and survival. CTCs were analyzed using the FDA approved CellSearch© system (Menarini Silicon Biosystems).ResultsIn the overall cohort, median OS was 24.1 months (95% CI 18.4 – 29.9 months) and median PFS was 6.2 months (95% CI 5.2 – 7.2 months). In the everolimus cohort, median OS was 20.2 months (95% CI 17.4 – 23.0 months) and median PFS was 5.5 months (95% CI 4.3 – 6.7 months. In the ribociclib cohort, median OS was 32.6 months (95% CI 26.6 – 38.6 months) and median PFS was 8.5 months (95% CI cannot be calculated) Median number of CTCs at baseline for all patients was 6.0 (range 1 – 400 CTCs). CTC assessments at the end of study treatment were available for 46 patients, of whom 36 patients (78.3%) had to terminate study treatment prematurely, mostly due to progress. CTC clearance rate at the end of study treatment in the full patient cohort was 45.7%, and CTC clearance rates for the everolimus and ribociclib cohort were 37.8% and 77.8%, respectively. Overall, patients with CTC clearance at the end of study treatment had significantly better PFS (hazard ratio 0.44, 95% CI 0.20 - 0.94, p = 0.035) and OS (hazard ratio 0.31, 95% CI 0.14 – 0.68, p = 0.002) than patients with CTCs.ConclusionsCTC clearance at the end of study treatment is associated with improved outcome and might be used to assess treatment response.Clinical trial identificationEudraCT 2013-001269-18, NCT02035813.Legal entity responsible for the studyUniversitätsklinikum Ulm (AöR), Albert-Einstein-Allee 29, D-89081 Ulm.FundingFinancial support for DETECT-IVa was provided by Amgen, Pierre Fabre, Menarini, Novartis and TEVA.DisclosureT.N. Fehm: Financial Interests, Personal, Other, Honoraria: Medconcept, Onkowissen, FOMF. F. Schochter: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, GSK, MSD, Clovis, Eisai; Financial Interests, Personal, Other, Travel expenses: MSD, AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Karyopharm. B. Rack: Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Research Grant: Lilly, BMS, Eisai, Menarini, Novartis, Roche, Inivata. P. Wimberger: Financial Interests, Personal, Research Funding: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche Pharma, Clovis, Lilly; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead, Daiichi Sankyo. M. Banys- Paluchowski: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Medical, Syantra, resitu, Pierre Fabre, ExactSciences; Financial Interests, Personal, Financially compensated role: EndoMag, Mammotome, MeritMedical, Sirius Medical, Gilead, Hologic, ExactSciences; Financial Interests, Personal, Other, Travel expenses: Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, Daiichi Sankyo, Roche. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, Astrazeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Sanofi Aventis, Medac, Menarini, Veracyte; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen, Gilead, Mylan; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Local PI: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v. J. Blohmer: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, MSD, Novartis, Pfizer, Roche Pharma, Eisai, Lilly, Gilead, Daichii Sankyo. A.D. Hartkopf: Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, Lilly, MSD, AstraZeneca, Daiichi Sankyo, Seagen, GSK, ExactScience, Gilead, Menarini Stemline, Pfizer, Eisai; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Lilly, MSD, AstraZeneca, Seagen, GSK, ExactScience, Riemser, TEVA, Onkowissen, Gilead, Menarini Stemline, Pfizer, Amgen, Pierre Fabre, Eisai, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Novartis, MSD, AstraZeneca, GSK, ExactScience, Riemser, Teva, Onkowissen, Gilead, Menarini Stemline, Pfizer, Amgen, Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, Travel expenses: Roche, Novartis, Lilly, AstraZeneca, GSK, ExactScience, Gilead, Menarini Stemline, Pfizer, Daiichi Sankyo. S. Heublein: Financial Interests, Personal, Research Funding, Honoraria: Clovis Oncology, GSK, Novartis, Roche, AstraZeneca, Pfizer; Financial Interests, Personal, Advisory Board: Novartis, GSK, Merck Sharp & Dohme Corporation. J. Huober: Financial Interests, Personal, Other, Honoraria: Lilly, Novartis, Roche, Pfizer, AstraZeneca, Seagen, Gilead, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor: Lilly, Novartis, Roche, Pfizer, AstraZeneca, Gilead, Daiichi Sankyo; Financial Interests, Personal, Other, Travel expenses: Roche, Novartis, Daiichi Sankyo, Gilead. K. Pantel: Financial Interests, Personal, Advisory Board, Expert Input Forum: MSD; Financial Interests, Personal, Advisory Board, Research Presentation and Discussion: Menarini; Financial Interests, Personal, Invited Speaker, Research Presentation and Discussion: Abcam, Ipsen Pharma, Medac, Agena; Financial Interests, Personal, Advisory Board, Advisory Board: Hello Healthcare, Sanofi; Financial Interests, Institutional, Other: Angle plc; Financial Interests, Institutional, Other, UKE - European Liquid Biopsy Society (ELBS): ELBS; Financial Interests, Institutional, Other, Clinical study: Böhringer Ingelheim; Financial Interests, Institutional, Other, EFPIA Partners of EU/IMI Cancer-ID consortium: IMI JT Cancer ID. A. Schneeweiss: Financial Interests, Personal, Research Grant: Celgene, Roche, AbbVie; Financial Interests, Personal, Other, Travel Expenses: Celgene, Roche, Pfizer; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Roche, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen, Pierre Fabre. T.W.P. Friedl: Financial Interests, Personal, Other, Honoraria: Lilly, Novartis. V. Mueller: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Lilly, Medscape, Gilead, Pierre Fabre, iMED Institut; Financial Interests, Personal, Advisory Board: Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline; Financial Interests, Institutional, Local PI: Novartis, Roche, Seagen, Genentech, AstraZeneca; Non-Financial Interests, Leadership Role: AGO German Breast Cancer Guideline Group. 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.