Abstract 101P
Background
Despite its crucial role in guiding clinical choices and trial eligibility for patients (pts) with hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (BC), the endocrine sensitive (ES) or primary (1ER)/secondary (2ER) resistant classification is largely based on expert opinion and no proper evidence exists to support its possible prognostic and clinical impact.
Methods
This analysis included individual pts-level data from 4 adjuvant phase III randomized trials by MIG and GIM study groups. The impact of ER/ES classification on overall survival (mOS, defined as time between date of distant relapse and death) was assessed in both univariate and multivariate Cox proportional hazards models.
Results
Between November 1992 and July 2012, 6612 pts with HR+/HER2- BC were randomized in 4 trials. Median follow-up was 9.1 years (IQR 5.6-15.0). In the whole cohort, the estimated hazard of recurrence raised constantly during the first 15 years from diagnosis, being more pronounced during the first 2 years and less after year 7. Among 493 pts with a distant relapse as first recurrence, 72 (14.6%), 207 (42.0%) and 214 (43.4%) were classified as having 1ER, 2ER and ES, respectively. Pts with 1ER were significantly more likely to be younger, to have N2/N3 nodal status, grade 3 tumors and to develop visceral metastases. Site of first distant relapse was significantly different between the 3 groups. In pts with 1ER, 2ER and ES breast cancer, median mOS was 27.2, 38.4 and 43.2 months, respectively (p=0.05). As compared to pts with ES disease, a significantly higher risk of death was observed in those with 1ER (adjusted [a] HR 1.57; 95% CI 1.08-2.28) and 2ER (aHR 1.25; 95% CI 0.94-1.67).
Conclusions
This large analysis with long-term follow-up provides evidence on the prognostic and clinical impact of the currently adopted ER/ES classification in pts with HR+/HER2- advanced BC. This classification may be considered a valid tool to guide clinical decision-making and to design future trials in the metastatic setting.
Legal entity responsible for the study
GIM (Gruppo Italiano Mammella).
Funding
Has not received any funding.
Disclosure
M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Institutional, Invited Speaker, 2-year research grant paid to my Institution: Gilead. G. Bisagni: Financial Interests, Advisory Board: PharmaMar, GSK. S. de Placido: Financial Interests, Invited Speaker: Novartis, Roche, Celgene, Bristol Myers Squibb, AstraZeneca, Pfizer, Lilly, Eisai, Seagen, Daiichi Sankyo, Clovis, GSK, MSD, Gilead, Exact Sciences. A. Fabi: Financial Interests, Invited Speaker: Roche, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, Seagen, MSD, Eli Lilly, Pierre Fabre, Epionpharma , Eisai. A. Michelotti: Financial Interests, Invited Speaker: Seagen, Gilead, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Eisai, Lilly, Istituto Gentili. M. Mansutti: Financial Interests, Invited Speaker: Roche, Novartis, Lilly, Pfizer, MSD, Gilead, Seagen, AstraZeneca, Gentili. A. Russo: Financial Interests, Invited Speaker: Brystol, Pfizer, Bayer, Kyowa Kirin, Ambrosetti, MSD, Roche Diagnostic. F. Montemurro: Financial Interests, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Seagen, MSD, Eli Lilly, Pierre Fabre, Novartis. A. Frassoldati: Financial Interests, Invited Speaker: Roche, AstraZeneca, Lilly, Novartis, Seagen, Daiichi Sankyo, Gilead. A. Turletti: Financial Interests, Invited Speaker: Novartis, Pfizer, Lilly, Roche. S. Tamberi: Financial Interests, Invited Speaker: Incyte MSD, Roche, Merck, AstraZeneca. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis, Seagen; Financial Interests, Personal, Invited Speaker: Zodiac, Libbs, Pierre Fabre, Lilly, Astra-Zeneca; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE; Financial Interests, Institutional, Invited Speaker: MSD, ABCSG, Nektar, Gilead, Immunomedics, Synthon, Odonate Therapeutics; Financial Interests, Invited Speaker, Chair of the Gilead Sciences Research Scholars Program in Solid Tumours: Gilead; Financial Interests, Invited Speaker, Aphinity, Lorelei, Impassion03: Roche; Financial Interests, Invited Speaker, AURORA: Breast International Group; Financial Interests, Invited Speaker, Olympia: Astra-Zeneca; Financial Interests, Personal, Other, Travel grant: Astra-Zeneca; Non-Financial Interests, Advisory Role, Member of the cardio-oncology council: European Society for Cardiology (ESC); Non-Financial Interests, Advisory Role, Belgium governmental institution for cancer: KCE; Non-Financial Interests, Other, Editorial board member: ESMO Open; Non-Financial Interests, Advisory Role: Anticancer Fund. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; 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 SrL; 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 srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead; Financial Interests, Personal, Other, Interview: Infomedica srl; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli lilly; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. All other authors have declared no conflicts of interest.