Abstract 229P
Background
The combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and endocrine therapy (ET) is the standard of care for patients (pts) with HR+/HER2- advanced breast cancer (aBC).Although the efficacy and safety profile of CDK4/6i and ET have been widely assessed in phase II and III trials conducted globally, it is still unclear whether the response to CDK4/6i might vary among different ethnic groups. Remarkably, several data suggest that pharmacogenetics differences existing between ethnicities may influence the clinical benefit of hormone therapies, targeted therapies and immune checkpoint inhibitors.Therefore, we aimed to evaluate the treatment efficacy of ET with and without CDK4/6i by comparing outcomes in Asian and non-Asian subgroups included in the prementioned clinical trials.
Methods
This meta-analysis included the most recent randomized trials published data systematically reviewed from PubMed, Embase, Web of Science, Cochrane CENTRAL or presented as abstracts or oral presentation at the ESMO, ASCO, and SABCS international congresses. We included trials comparing CDK4/6i in combination with ET versus placebo plus ET. Progression-free survival (PFS) and overall survival (OS) hazard ratios (HR) and 95% confidence intervals (CI) for the two subgroups of interest were extracted.
Results
Eleven trials accounting for 5129 pts were included in the present meta-analysis. The addition of CDK4/6i to ET resulted in a consistent PFS benefit in both Asian (HR:0.53 [95% CI 0.47-0.60], p<0.001) and non-Asian (HR:0.58 [95% CI 0.52-0.64], p<0.001) subgroups. Moreover, the combination of CDK4/6i+ET resulted in an OS improvement in both Asian (HR: 0.75 [95% CI 0.62-0.91], p= 0.003) and non-Asian (HR:0.81 [95% CI 0.73-0.89], p<0.001) pts.
Conclusions
The combination of CDK4/6i and ET significantly improved PFS and OS compared to ET alone for both Asian and non-Asian pts with HR+/HER- aBC. Although the magnitude of benefit appeared to be independent in Asian vs non-Asian ethnicity groups, it would be highly desirable to standardize ethnicity stratification criteria of pts in future trials to effectively estimate differences in treatment benefit.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Pagliuca: Other, Personal, Other, Travel expenses: Gilead. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed S.r.l.; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Invited Speaker, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Invited Speaker, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting S.r.l.; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo S.r.l.; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over S.r.l.; Financial Interests, Personal, Invited Speaker: Prex S.r.l, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead, GSK, Eisai, Stemline Menarini; Financial Interests, Personal, Other, Interview: Infomedica S.r.l.; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli Lilly, Gilead; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Financial Interests, Institutional, Invited Speaker: Gilead, Seagen; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. F. Puglisi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Gilead, Novartis, Exact Sciences, Lilly, MSD; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Daiichi Sankyo, Seagen; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Other: Lilly, Novartis, Pierre Fabre, Novartis, Menarini; Financial Interests, Personal, Advisory Board: MSD, Pierre Fabre, Gilead; Financial Interests, Personal and Institutional, Advisory Board: Menarini, Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Roche. M. Giuliano: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Eisai, MSD, Novartis, Pfizer, Seagen; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, travel expenses: AstraZeneca, Pfizer. G. Arpino: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Lilly, Eisai, AstraZeneca, Gilead, Seagen, Viatris, Exact Sciences, Daiichi Sankyo, Novartis; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Lilly, AstraZeneca, Novartis, Seagen, Daiichi Sankyo, Eisai, Gilead. M. De Laurentiis: Financial Interests, Personal, Invited Speaker: Eli Lilly, Menarini; Financial Interests, Personal, Other, travel expenses: Gilead, Roche, AstraZeneca, Novartis, Roche, Pfizer, Daiichi Sankyo, Eli Lilly, Genetic, Pierre Fabre, GSK, Exact Sciences, Tomalab, MSD, Eisai; Financial Interests, Personal, Advisory Board: Seagen, Eli Lilly, Novartis, Pierre Fabre, Sanofi, GSK, Gilead, AstraZeneca, Daiichi Sankyo, MSD, Roche, Eisai, Exact Sciences; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.