350MO - Omission of chemotherapy and addition of the CDK4/6 inhibitor ribociclib in HER2-positive and hormone-receptor positive metastatic breast cancer – Second interim efficacy analysis of the randomized phase III DETECT V trial

Background

In patients with HER2-positive metastatic breast cancer (MBC), chemotherapy in combination with dual HER2 targeted therapy with trastuzumab (T) and pertuzumab (P) is the standard of care first line therapy. However, the less toxic synergistic combination of dual HER2-targeted therapy plus endocrine therapy might offer a treatment option for patients with HER2-positive and hormone-receptor (HR) positive MBC.

Methods

In the multicenter phase III DETECT V trial, 271 patients with HER2-positive and HR-positive MBC were randomized to receive T and P combined with either physicians’ choice endocrine therapy or chemotherapy followed by maintenance therapy with T, P and endocrine therapy. After 124 enrolled patients, the study was amended with the addition of the CDK4/6 inhibitor ribociclib to endocrine therapy in both arms. Objectives were to compare efficacy and tolerability between the chemotherapy-free and chemotherapy-containing treatment arm; furthermore, the effect of adding ribociclib to both treatment arms should be evaluated. Here we report results of the second interim efficacy analysis with data cut off April 3rd 2024 (54 patients still in the follow up period).

Results

Overall survival (OS) and progression-free survival (PFS) did not differ between patients receiving chemotherapy-free and chemotherapy-containing treatment (median OS not reached vs. 46.1 months, hazard ratio 1.07, 95% CI 0.65 – 1.77, p = 0.79; median PFS 19.1 vs. 22.4 months, hazard ratio 1.19, 95% CI 0.84 – 1.69, p = 0.34). However, both OS and PFS were significantly improved in patients receiving ribociclib in addition to chemotherapy or endocrine therapy based treatment (median OS not reached vs. 46.1 months, hazard ratio 0.42, 95% CI 0.24 – 0.74, p = 0.002; median PFS 27.2 vs. 15.6 months, hazard ratio 0.52, 95% CI 0.37 – 0.75, p < 0.001).

Conclusions

Our preliminary results suggest that chemotherapy-free treatment for patients with HER2-positive and HR-positive MBC might be an effective alternative, while the addition of ribociclib may further improve survival.

Clinical trial identification

NCT: 02344472 EudraCT: 2014-002249-22.

Editorial acknowledgement

Legal entity responsible for the study

Detect Study Group.

Funding

Financial support for the DETECT V study was provided by BMS, Eisai, Menarini, Novartis and Roche.

Disclosure

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. 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. A.M.B. de Gregorio: Financial Interests, Advisory Board: AstraZeneca, Daiichi Sankyo, Pfizer, MSD, Menarini Stemline, Novartis, Roche, Seagen, Gilead, Lilly; Financial Interests, Other, Travel grants: AstraZeneca; Financial Interests, Other, travel grants: Daiichi Sankyo. T. Decker: Financial Interests, Personal, Advisory Board: Novartis, Lilly, Pfizer, AstraZeneca. A.D. Hartkopf: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Advisory Board: MSD, AstraZeneca, GSK, ExactScience, Riemser, Teva, Onkowissen, Gilead, Menarini Stemline, Pfizer, Amgen, Pierre Fabre, Daiichi Sankyo; Financial Interests, Speaker’s Bureau: Roche, Novartis, Lilly, MSD, AstraZeneca, Daiichi Sankyo, Seagen, GSK, ExactScience, Gilead, Menarini Stemline, Pfizer, Eisai; Financial Interests, 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, Other, Travel grant: Roche, Lilly, GSK, ExactScience, Gilead, Menarini Stemline, Pfizer, Daiichi Sankyo; Financial Interests, Other, travel grant: Novartis, AstraZeneca. M. Schmidt: Financial Interests, Personal, Advisory Board: AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, GILEAD, Stemline; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, Novartis, Pierre Fabre; Financial Interests, Personal, Trial Chair: Pfizer. P. Wimberger: Financial Interests, Research Funding: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche, Clovis, Lilly; Financial Interests, Other, Honoraria: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche, Clovis, Teva, Eisai, Lilly, Gilead, Daiichi Sankyo; Financial Interests, Advisory Board: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche, Clovis, Teva, Eisai, Lilly, Gilead, Daiichi Sankyo. T. Engler: Financial Interests, Advisory Board: AstraZeneca, Daiichi Sankyo, GSK, Gilead, Novartis, Lilly, Pfizer, Pierre Fabre, MSD, Menarini Stemline. M. Banys- Paluchowski: Financial Interests, Other, Honoraria: Roche, Novartis, Pfizer, pfm, Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Medical, Syantra, resitu, Pierre Fabre, ExactSciences; Financial Interests, Other, Study support: EndoMag, Mammotome, Merit Medical, Sirius Medical, Gilead, Hologic, ExactSciences; Financial Interests, Other, Travel grants: Lilly, ExactSciences, Daiichi Sankyo, Roche; Financial Interests, Other, Travel grant: Pierre Fabre, Pfizer. 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. B. Rack: Financial Interests, Other, Honoraria: Novartis; Financial Interests, Research Grant: Lilly, BMS, Eisai, Menarini, Novartis, Roche, Inivata. A. Schneeweiss: Financial Interests, Research Grant: Celgene, Roche, Abbvie; Financial Interests, Personal, Other, Travel grants: Celgene, Roche, Pfizer, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Celgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen, Pierre Fabre. J. Blohmer: Financial Interests, Advisory Board: AstraZeneca, MSD, Novartis, Pfizer, Roche, Eisai, Lilly, Gilead, Daiichi Sankyo. J. Huober: Financial Interests, Other, Honoraria: Lilly, Novartis, Roche, Pfizer, AstraZeneca, Seagen, Gilead, Daiichi Sankyo; Financial Interests, Advisory Role: Lilly, Novartis, Roche, Pfizer, AstraZeneca, Gilead, Daiichi Sankyo; Financial Interests, Other, Travel grants: Roche, Novartis, Gilead, Daiichi Sankyo. 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. T.W.P. Friedl: Financial Interests, Personal, Other, Honoraria: Lilly, Novartis. F. Schochter: Financial Interests, Other, Honoraria: Roche, AstraZeneca, GSK, MSD, Clovis, Eisai; Financial Interests, Other, Travel grants: MSD, AstraZeneca; Financial Interests, Research Grant: AstraZeneca, Roche, Karyopharm. All other authors have declared no conflicts of interest.