Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies
Aleix Prat, Anwesha Chaudhury, Nadia Solovieff, Laia Paré, Débora Martinez, Nuria Chic, Olga Martínez-Sáez, Fara Brasó-Maristany, Agnes Lteif, Tetiana Taran, Naveen Babbar, Fei Su, Aleix Prat, Anwesha Chaudhury, Nadia Solovieff, Laia Paré, Débora Martinez, Nuria Chic, Olga Martínez-Sáez, Fara Brasó-Maristany, Agnes Lteif, Tetiana Taran, Naveen Babbar, Fei Su
Abstract
Purpose: 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.
Methods: 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.
Results: 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 (P < .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; P < .0001), LumB (HR, 0.52; P < .0001), LumA (HR, 0.63; P = .0007), and normal-like (HR, 0.47; P = .0005) subtypes derived benefit from RIB. Patients with basal-like subtype (n = 30) did not derive benefit from RIB (HR, 1.15; P = .77).
Conclusion: 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.
Trial registration: ClinicalTrials.gov NCT01958021 NCT02422615 NCT02278120.
Conflict of interest statement
Aleix PratHonoraria: Nanostring Technologies, Bristol Myers Squibb, Novartis, Merck Sharp & Dohme, Pfizer, Roche, Lilly, Oncolytics Biotech, Amgen, Daiichi Sankyo, PUMA, Boehringer Anwesha ChaudhuryEmployment: Novartis Nadia SolovieffEmployment: NovartisStock and Other Ownership Interests: Novartis Nuria ChicTravel, Accommodations, Expenses: Novartis Agnes LteifEmployment: NovartisStock and Other Ownership Interests: Novartis Tetiana TaranEmployment: NovartisStock and Other Ownership Interests: Novartis Naveen BabbarEmployment: NovartisStock and Other Ownership Interests: Novartis Fei SuEmployment: NovartisStock and Other Ownership Interests: NovartisNo other potential conflicts of interest were reported.
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Source: PubMed