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.

BACKGROUND: The MONALEESA-2, -3, -7 trials demonstrated statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) benefits with ribociclib + endocrine therapy (ET) vs ET alone in hormone receptor-positive, human epidermal growth factor receptor 2-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.

PATIENTS AND METHODS: 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.

RESULTS: Overall, 990 tumors (among 2066 patients) from ribociclib (n=580) and placebo (n=410) arms were profiled. Subtype distribution was luminal A, 54.5%; luminal B, 28.0%; HER2E, 14.6%; 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=.018), luminal B (HR, 0.69; P=.023), and luminal A (HR, 0.75; P=.021) subtypes derived OS benefit with ribociclib. Patients with basal-like subtype did not derive benefit from ribociclib (HR, 1.92; P=.137); however, patient numbers were small (n=28).

CONCLUSION: The prognostic value of intrinsic subtypes for OS was confirmed in this pooled analysis of the MONALEESA trials (largest data set 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.