Data from Intrinsic Subtype and Overall Survival of Patients with Advanced HR<sup>+</sup>/HER2<sup>−</sup> Breast Cancer Treated with Ribociclib and ET: Correlative Analysis of MONALEESA-2, -3, -7

Abstract

<div>AbstractPurpose:<p>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<sup>+</sup>/HER2<sup>−</sup>) 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.</p>Experimental Design:<p>Tumor samples from MONALEESA-2, -3, -7 underwent PAM50-based subtyping. The relationship between subtypes and OS was assessed using univariable and multivariable Cox proportional hazards models. Multivariable models were adjusted for clinical prognostic factors.</p>Results:<p>Overall, 990 tumors (among 2,066 patients) from ribociclib (<i>n</i> = 580) and placebo (<i>n</i> = 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; <i>P</i> = 0.018), luminal B (HR, 0.69; <i>P</i> = 0.023), and luminal A (HR, 0.75; <i>P</i> = 0.021) subtypes derived OS benefit with ribociclib. Patients with basal-like subtype did not derive benefit from ribociclib (HR, 1.92; <i>P</i> = 0.137); however, patient numbers were small (<i>n</i> = 28).</p>Conclusions:<p>The prognostic value of intrinsic subtypes for OS was confirmed in this pooled analysis of the MONALEESA trials (largest dataset in HR<sup>+</sup>/HER2<sup>−</sup> ABC). While basal-like subtype did not benefit, a consistent OS benefit was observed with ribociclib added to ET across luminal and HER2E subtypes.</p></div>