243P - Prognosis of patients with hormone receptor-positive/HER2-negative early breast cancer according to monarchE and NATALEE trials risk categories: Patient-level analysis of Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) randomised trials

Background

The monarchE and NATALEE trials employed different criteria to define patients at high-risk of recurrence, but prognostic differences between these groups have not yet been explored. Therefore, main objective of this analysis is to assess the prognosis of patients according to monarchE and NATALEE trials risk categories.

Methods

Patients with hormone receptor-positive (HR+)/ HER2-negative (HER2-) early breast cancer (eBC) enrolled in the adjuvant phase III MIG1, GIM2, and GIM3 trials were categorized into high-risk cohort (HRC) and non-HRC (nHRC) according to the enrolment criteria of the two trials. Subsequently, they were further classified in three different cohorts: concordant nHRC (nHRC for both trials), discordant HRC (HRC for only one trial), and concordant HRC (HRC for both trials). The outcomes of interest were disease-free survival (DFS) and overall survival (OS).

Results

Among 7,002 patients enrolled in the three trials, 4,795 had HR+/HER2- eBC, of whom 1,343 (28.0%) and 2,689 (56.1%) were classified in the HRC according to the monarchE and NATALEE trials, respectively. At a median follow-up of 7.04 years (y), 7-y DFS was 87% and 89% in the nHRC and 69% and 76% in the HRC according to monarchE and NATALEE trials, respectively. All patients included in monarchE HRC were also included in NATALEE HRC, while 1,346 (28.1%) patients were solely classified in the NATALEE HRC, and 2,106 (43.9%) were in the nHRC category for both trials. The 7-y DFS was 89%, 84% and 69% in concordant nHRC, discordant HRC, and concordant HRC, respectively (discordant HRC vs. concordant nHRC Hazar Ratio (HR) 1.45, 95%CI 1.22-1.73; concordant HRC vs. concordant nHRC HR 2.97, 95%CI 2.53-3.48; p<0.001). The 7-y OS was 96% in concordant nHRC, 95% in discordant HRC, and 84% in concordant HRC (discordant HRC vs. concordant nHRC HR: 1.52, 95%CI 1.16-1.98; concordant HRC vs. concordant nHRC HR 3.38, 95%CI 2.66-4.29; p<0.001).

Conclusions

Patients in the HRC according only to the NATALEE trial exhibit a slightly worse prognosis compared to patients in the nHRC, but much better prognosis compared to HRC by the monarchE trial.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Italian Association for Cancer Research ("Associazione Italiana per la Ricerca sul Cancro", AIRC; IG 2017/20760) and the Italian Ministry of Health (5 × 1000 funds, years 2021-2022).

Disclosure

E. Blondeaux: Financial Interests, Institutional, Research Grant, Research grant to my Institution for a research project: Gilead Science. G. Arpino: Financial Interests, Personal, Advisory Role: Roche, Pfizer, Novartis; Financial Interests, Personal, Invited Speaker: Lilly, Eisai, Novartis, Amgen. C. De Angelis: Financial Interests, Personal, Advisory Role, speaker honoraria: Roche, Lilly, Novartis, Pfizer, Seagen, Gilead, GSK; Financial Interests, Personal, Advisory Role: Astrazeneca, Daiichi Sankyo; Financial Interests, Institutional, Research Funding: Novartis, GILEAD, Daiichi Sankyo. M. De Laurentiis: Financial Interests, Personal, Advisory Board: Sanofi, GSK, MSD, Daiichi Sankyo, Seagen, Pfizer, Roche, Novartis, Eli Lilly, AstraZeneca; Financial Interests, Personal, Advisory Role: Celltrion, Organon. R. Caputo: Financial Interests, Advisory Board: Menarini, Pierre-Fabre, Veracyte, Exact Science, AstraZeneca, Daichii Sankyo, MSD, Seagen; Financial Interests, Advisory Board, and Travel accomodation, registration for international congresses: Gilead, Novartis, Eli Lilly. A. Fabi: Financial Interests, Advisory Board, and Payment or honoraria: Exact Science, AstraZeneca, Seagen, Gilead, Pierre Fabre, MSD, Pfizer, Lilly, Novartis, Roche; Financial Interests, Advisory Board: Sophos, Dompè. F. Puglisi: Financial Interests, Advisory Role: Viatris, Takeda, Seagen, Roche, Pfizer, Pierre Fabre, Novartis, MSD, Menarini, Ipsen, Gilead, Exact Sciences, Eli Lilly, Eisai, Celgene, Daichii Sankyo, AstraZeneca, Amgen. E. Agostinetto: Financial Interests, Personal, Advisory Role: Eli Lilly, Sandoz, AstraZeneca; Financial Interests, Institutional, Research Funding: Gilead; Financial Interests, Personal, Other, Support for attending medical conferences: Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo, AstraZeneca. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis, Seagen, MSD; Financial Interests, Personal, Invited Speaker: Zodiac, Libbs, Pierre Fabre, Lilly, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Other, Chair of the Gilead Sciences Research Scholars Program in Solid Tumours: Gilead Sciences; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE; Financial Interests, Institutional, Local PI: MSD, ABCSG, Nektar, Gilead, Immunomedics, Synthon, Odonate Therapeutics; Financial Interests, Steering Committee Member, ASCENT 04: Gilead; Financial Interests, Steering Committee Member, Aphinity, Lorelei, Impassion03: Roche; Financial Interests, Steering Committee Member, AURORA: Breast International Group; Financial Interests, Steering Committee Member, Olympia: AstraZeneca; Financial Interests, Personal, Other, Travel grant: AstraZeneca; Non-Financial Interests, Advisory Role, Member of the cardio-oncology council: European Society of 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; Non-Financial Interests, Leadership Role, President 2023-2026: Belgian Society of Medical Oncology (BSMO). M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead, Menarini, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche, AstraZeneca, Menarini, Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Personal, Other, Travel grant to attend ASCO 2023 and ASCO 2024: Daiichi Sankyo; Financial Interests, Personal, Other, Travel grant to attend SABCS 2023: Roche; Financial Interests, Institutional, Coordinating PI, 2-year research grant paid to my Institution: Gilead; Non-Financial Interests, Leadership Role, Chair of the ESMO Young Oncologists Committee from 01/2023 to 12/2024: ESMO; Non-Financial Interests, Member of Board of Directors, Member of the national council of the Italian Association of Medical Oncology (AIOM): AIOM. 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, Writing Engagement, 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, Writing Engagement, 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, GSK, Eisai, Stemline Menarini; 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, 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, Local PI: Gilead, Seagen; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. All other authors have declared no conflicts of interest.