358P - Everolimus or ribociclib in patients with HER2-negative, hormone-receptor positive metastatic breast cancer and circulating tumor cells: Results from DETECT IVa

Background

DETECT-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 1^st – 3^rd 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.

Methods

DETECT 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).

Results

In 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.

Conclusions

CTC clearance at the end of study treatment is associated with improved outcome and might be used to assess treatment response.

Clinical trial identification

EudraCT 2013-001269-18, NCT02035813.

Editorial acknowledgement

Legal entity responsible for the study

Universitätsklinikum Ulm (AöR), Albert-Einstein-Allee 29, D-89081 Ulm.

Funding

Financial support for DETECT-IVa was provided by Amgen, Pierre Fabre, Menarini, Novartis and TEVA.

Disclosure

T.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.