Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies

• Published in: Journal of clinical oncology Vol. 39; no. 13; pp. 1458 - 1467
• Main Authors: Prat, Aleix, Chaudhury, Anwesha, Solovieff, Nadia, Paré, Laia, Martinez, Débora, Chic, Nuria, Martínez-Sáez, Olga, Brasó-Maristany, Fara, Lteif, Agnes, Taran, Tetiana, Babbar, Naveen, Su, Fei
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 01-05-2021
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - metabolism; Bone Neoplasms - drug therapy; Bone Neoplasms - metabolism; Bone Neoplasms - secondary; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Double-Blind Method; Female; Follow-Up Studies; Humans; ORIGINAL REPORTS; Prognosis; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Retrospective Studies; Survival Rate
• DOI: 10.1200/JCO.20.02977
• EISSN: 1527-7755
• ISSN: 0732-183X

The prognostic and predictive value of intrinsic subtypes in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer treated with endocrine therapy and ribociclib (RIB) is currently unknown. We evaluated the association of intrinsic subtypes with progression-free survival (PFS) in the MONALEESA trials.
A retrospective and exploratory PAM50-based analysis of tumor samples from the phase III MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials was undertaken. The prognostic relationship of PAM50-based subtypes with PFS and risk of disease progression by subtype and treatment were evaluated using a multivariable Cox proportional hazards model, adjusting for age, prior chemotherapy, performance status, visceral disease, bone-only metastases, histological grade, number of metastatic sites, prior endocrine therapy, and de novo metastatic disease.
Overall, 1,160 tumors from the RIB (n = 672) and placebo (n = 488) cohorts were robustly profiled. Subtype distribution was luminal A (LumA), 46.7%; luminal B (LumB), 24.0%; normal-like, 14.0%; HER2-enriched (HER2E), 12.7%; and basal-like, 2.6% and was generally consistent across treatment arms and trials. The associations between subtypes and PFS were statistically significant in both arms (
< .001). The risks of disease progression for LumB, HER2E, and basal-like subtypes were 1.44, 2.31, and 3.96 times higher compared with those for LumA, respectively. All subtypes except basal-like demonstrated significant PFS benefit with RIB. HER2E (hazard ratio [HR], 0.39;
< .0001), LumB (HR, 0.52;
< .0001), LumA (HR, 0.63;
= .0007), and normal-like (HR, 0.47;
= .0005) subtypes derived benefit from RIB. Patients with basal-like subtype (n = 30) did not derive benefit from RIB (HR, 1.15;
= .77).
In this retrospective exploratory analysis of hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer, each intrinsic subtype exhibited a consistent PFS benefit with RIB, except for basal-like.