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. 2025 Jun 1;117(6):1198-1208.
doi: 10.1093/jnci/djaf031.

Prognostic implications of risk definitions from the monarchE and NATALEE trials

Luca Arecco  1   2 , Eva Blondeaux  3 , Marco Bruzzone  3 , Grazia Arpino  4 , Carmine De Angelis  5 , Michelino De Laurentiis  6 , Roberta Caputo  6 , Alessandra Fabi  7 , Valeria Sanna  8 , Stefania Gori  9 , Fabio Puglisi  10   11 , Luca Boni  3 , Simone Nardin  1   12 , Irene Giannubilo  1   12 , Marta Perachino  1   12 , Roberto Borea  1   12 , Elisa Agostinetto  2 , Evandro de Azambuja  2 , Matteo Lambertini  1   12 , Lucia Del Mastro  1   12
Affiliations

Prognostic implications of risk definitions from the monarchE and NATALEE trials

Luca Arecco et al. J Natl Cancer Inst. .

Abstract

Background: The monarchE and NATALEE trials employed different high-risk inclusion criteria. The main objective is to assess prognostic differences based on their inclusion criteria.

Methods: Patients with hormone receptor-positive/HER2-negative early breast cancer enrolled in the phase III Mammella InterGruppo (MIG) 1, Gruppo Italiano Mammella (GIM) 2, and GIM3 trials were categorized as high-risk cohort (HRC) and low-risk cohort (LRC) according to the inclusion criteria of monarchE and NATALEE trials. Subsequently, they were further classified in 3 different cohorts: concordant LRC (low risk for both trials), discordant risk cohort (high risk for only one trial), and concordant HRC (high risk for both trials). Main outcomes were disease-free survival (DFS) and overall survival (OS).

Results: Among 4795 patients, 1343 (28.0%) and 2689 (56.1%) were classified as HRC according to the monarchE and NATALEE, respectively. At a median follow-up of 7.0 years (y), 7-y DFS was 87% and 89% in the LRC and 69% and 76% in the HRC according to monarchE and NATALEE, respectively. The 7-y DFS was 89%, 84%, and 69% in concordant LRC, discordant cohort, and concordant HRC, respectively (discordant cohort vs concordant LRC: hazard ratio [HR] = 1.45, 95% CI = 1.22 to 1.73; concordant HRC vs concordant LRC: HR = 2.97, 95% CI = 2.53 to 3.48; P < .001). The 7-y OS was 96% in concordant LRC, 95% in discordant cohort, and 84% in concordant HRC (discordant cohort vs concordant LRC: HR = 1.52, 95% CI = 1.16 to 1.98; concordant HRC vs concordant LRC: HR = 3.38, 95% CI = 2.66 to 4.29; P < .001).

Conclusions: Patients in the concordant HRC showed statistically and clinically significant poorer prognoses compared with patients in the discordant risk and concordant LRC.

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Conflict of interest statement

L.A. reported travel grants from AstraZeneca. E.B. reported receiving research funding (to her institution) from Gilead, speaker fees from Eli Lilly. G.A. reported consulting or advisory roles for Roche, Pfizer, Lilly, Eisai, Novartis, and Amgen; research funding from Roche, Pfizer, and Novartis; and travel, accommodation, or expenses from Roche, Pfizer, Lilly, Eisai, Novartis, and Amgen. C.D.A. reported advisory role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Daiichi-Sankyo, Gilead, and GSK and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, GSK, GILEAD, and Daiichi-Sankyo. Travel grants from Gilead and research support (to the Institution) from Novartis, GILEAD, and Daiichi-Sankyo outside the submitted work. M.D.L. reported payment or honoraria, meeting, or travel support (or both), and advisory board participation for AstraZeneca, Eli Lilly, Novartis, Roche, Pfizer, Seagen, Daiichi Sankyo, MSD, GSK, and Sanofi; and payment or honoraria from Celltrion and Organon. R.C.: consulting or advisory role: Eli Lilly, Novartis, Gilead, Seagen, MSD, Daiichi Sankyo, Astra Zeneca, Exact Science, Veracyte, Pierre-Fabre, Menarini. Travel accommodation, registration for international congresses: Novartis, Lilly, Gilead. A.F. reported independent grants or contracts from Pfizer, Gilead; consulting fees from Roche, Novartis, Lilly, Pfizer, MSD, Dompè, Pierre Fabre, Sophos, Gilead, Seagen, Astra Zeneca, Exact Science; payment or honoraria from Roche, Novartis, Lilly, Pfizer, MSD, Pierre Fabre, Gilead, Seagen, Astra Zeneca, Exact Science; support for attending meetings and/or travel from Roche, Novartis, Lilly, Pfizer, MSD, Pierre Fabre, Gilead, Seagen, Astra Zeneca, Exact Science; participation on a Data Safety Monitoring Board or Advisory Board for Roche, Novartis, Lilly, Pfizer, MSD, Gilead, Seagen, Astra Zeneca, Exact Science; leadership or fiduciary role in European Society for Medical Oncology (ESMO), Associazione Italiana Oncologia Medica. F.P. reported having an advisory role for and receiving speaker honoraria, travel grants, and research grants from Amgen, AstraZeneca, Daiichi Sankyo, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, and Viatris. E.A. reported Advisory Board and/or Honoraria: Eli Lilly, AstraZeneca, Abscint, Bayer; Research grant to my Institution from Gilead; Meeting/Travel grant: Novartis, Roche, Eli Lilly, Daiichi Sankyo, AstraZeneca, Abscint, Menarini (all outside the submitted work). E.d.A. reported honoraria and/or advisory board from Roche/GNE, Novartis, Seagen, Zodiac, Libbs, Pierre Fabre, Lilly, AstraZeneca, MSD, Gilead Sciences; travel grants from Roche/GNE and Astra-Zeneca; Research grant to my institution from Roche/GNE, Astra-Zeneca, and GSK/Novartis, Gilead Sciences; nonfinancial: ESMO director of Membership 2023-2025, BSMO President 2023-2026. M.L. reported having an advisory role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Pierre Fabre, and Exact Sciences; receiving speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Knight, Ipsen, and AstraZeneca; receiving travel grants from Gilead, Roche, and Daiichi Sankyo; receiving research funding (to his institution) from Gilead; and having nonfinancial interests as the chair of the ESMO Young Oncologists Committee and as a member of the national council of the Italian Association of Medical Oncology. L.D.M. reported grants from Eli Lilly, Novartis, Roche, Daiichi Sankyo, Seagen, AstraZeneca, Gilead, and Pierre Fabre; receiving consulting fees from Eli Lilly, Gilead, and Daiichi Sankyo; receiving speaker honoraria from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen, GSK, and Agendia-Stemline; receiving travel grants from Roche, Pfizer, Eisai, Daiichi Sankyo, and AstraZeneca; and having an advisory role for Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sakyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, AstraZeneca, Agendia, GSK, and Seagen. All the other authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
CONSORT diagram of MIG/GIM individual patient-level data. Abbreviations: GIM2 = Gruppo Italiano Mammella 2 trial; GIM3 = Gruppo Italiano Mammella 3 trial; HR = hormone receptor; MIG1 = Mammella InterGruppo 1 trial.
Figure 2.
Figure 2.
Survival outcomes of MIG/GIM patients considered at low risk and high risk of recurrence according to the monarchE and NATALEE trials inclusion criteria. A) Disease-free survival according with monarchE trial. B) Disease-free survival according with NATALEE trial. Abbreviations: GIM = Gruppo Italiano Mammella; MIG = Mammella InterGruppo.
Figure 3.
Figure 3.
Prognosis of patients divided into concordant low-risk cohort, discordant risk cohort, and concordant high-risk cohort according to monarchE and NATALEE trials inclusion criteria. A) Disease-free survival. B) Distant relapse-free survival. C) Overall survival.
See this image and copyright information in PMC

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