In an analysis of several phase III MONALEESA trials reported in the Journal of Clinical Oncology, Aleix Prat, MD, PhD, and colleagues found consistent progression-free survival benefits with the combination of ribociclib plus endocrine therapy vs placebo plus endocrine therapy across all intrinsic subtypes of hormone receptor (HR)-positive, HER2-negative advanced breast cancer—except for the basal-like subtype.
Study Details
The study involved PAM50-based analysis of tumor samples from the phase III placebo-controlled MONALEESA-2 (688 postmenopausal women randomly assigned to ribociclib plus letrozole or placebo plus letrozole), MONALEESA-3 (726 postmenopausal women and men randomly assigned 2:1 to ribociclib plus fulvestrant or placebo plus fulvestrant), and MONALEESA-7 trials (672 premenopausal or perimenopausal women randomly assigned to ribociclib or placebo with either tamoxifen or nonsteroidal aromatase inhibitor treatment, all with goserelin.)
Aleix Prat, MD, PhD
Key Findings
Overall, 1,160 tumors from the ribociclib/endocrine therapy (n = 672) and placebo/endocrine therapy (n = 488) cohorts had sufficient profiling for analysis. Intrinsic subtype distribution was luminal A in 46.7% of patients, luminal B in 24.0%, normal-like in 14.0%, HER2-enriched in 12.7%, and basal-like in 2.6%.
In analysis adjusting for clinical-pathologic variables, intrinsic subtype was independently associated with progression-free survival (P < .001) in both treatment cohorts.
In adjusted analysis among all patients, higher risk of disease progression was observed for patients with luminal B subtype (hazard ratio [HR] = 1.44, P = .00086), HER2-enriched subtype (HR = 2.31, P < .0001), and basal-like subtype (HR = 3.96, P < .0001) but not normal-like subtype (HR = 1.28, P = .056) compared with luminal A subtype.
Ribociclib was associated with a significant progression-free survival benefit across all subtypes, except the basal-like subtype. For the ribociclib/endocrine therapy vs placebo/endocrine therapy groups, median progression-free survival was 29.6 vs 19.5 months (HR = 0.63, P = .0007) for luminal A subtype, 22.2 vs 12.9 months (HR = 0.52, P < .0001) for luminal B subtype, 16.4 vs 5.5 months (HR = 0.39, P < .0001) for HER2-enriched subtype, 22.3 vs 11.1 months (HR = 0.47, P = .0005) for normal-like subtype, and 3.7 vs 3.6 months among the 30 patients with basal-like subtype (HR = 1.15, P = .77).
The investigators concluded: “In this retrospective exploratory analysis of HR-positive, HER2-negative advanced breast cancer, each intrinsic subtype exhibited a consistent progression-free survival benefit with ribociclib, except for basal-like.”
Dr. Prat is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Novartis, Instituto de Salud Carlos III, Breast Cancer Research Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.
