Intrinsic Subtype and Overall Survival of Patients with Advanced HR+/HER2_ Breast Cancer Treated with Ribociclib and ET: Correlative Analysis of MONALEESA-2, -3, -7

Aleix Prat, Nadia Solovieff, Fabrice André, Joyce O'Shaughnessy, David A. Cameron, Wolfgang Janni, Gabe S. Sonke, Yoon Sim Yap, Denise A. Yardley, Ann H. Partridge, Astrid Thuerigen, Juan Pablo Zarate, Agnes Lteif, Fei Su, Lisa A. Carey

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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    Résumé

    Purpose: The MONALEESA-2, -3, -7 trials demonstrated statistically significant and clinically meaningful progression-free survival and overall survival (OS) benefits with ribociclib plus endocrine therapy (ET) versus ET alone in hormone receptor-positive, HER2- negative (HR+/HER2_) advanced breast cancer (ABC). Understanding the association of intrinsic subtypes with survival outcomes could potentially guide treatment decisions. Here, we evaluated the association of intrinsic subtypes with OS in MONALEESA-2, -3, -7. Experimental Design:Tumor samples fromMONALEESA-2, -3, -7 underwent PAM50-based subtyping. The relationship between subtypes and OS was assessed using univariable and multivariable Cox proportional hazardsmodels.Multivariablemodels were adjusted for clinical prognostic factors. Results: Overall, 990 tumors (among 2,066 patients) from ribociclib (n = 580) and placebo (n = 410) arms were profiled. Subtype distribution was luminal A, 54.5%; luminal B, 28.0%; HER2-enriched (HER2E) 14.6%; and basal-like, 2.8%; and was consistent across treatment arms. The luminal A subtype had the best OS outcomes in both arms, while basal-like had the worst. Patients with HER2E (HR, 0.60; P = 0.018), luminal B (HR, 0.69; P = 0.023), and luminal A (HR, 0.75; P = 0.021) subtypes derived OS benefit with ribociclib. Patients with basal-like subtype did not derive benefit from ribociclib (HR, 1.92; P = 0.137); however, patient numbers were small (n = 28). Conclusions:The prognostic value of intrinsic subtypes for OS was confirmed in this pooled analysis of the MONALEESA trials (largest dataset in HR+/HER2_ ABC). While basal-like subtype did not benefit, a consistent OS benefit was observed with ribociclib added to ET across luminal and HER2E subtypes.

    langue originaleAnglais
    Pages (de - à)793-802
    Nombre de pages10
    journalClinical Cancer Research
    Volume30
    Numéro de publication4
    Les DOIs
    étatPublié - 15 févr. 2024

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