In-depth gene expression analysis of premenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with ribociclib-containing therapy in the Phase III MONALEESA-7 trial
Autor: | Marco Colleoni, Debu Tripathy, Paul Wheatley-Price, Wei He, Naveen Babbar, Louis W.C. Chow, Fabio Franke, Sherko Kuemmel, Nadia Harbeck, Saul Campos Gomez, Karen Rodriguez-Lorenc, Aditya Bardia, Seock-Ah Im, Sara A. Hurvitz, Fei Su, Kyung Hae Jung, Tetiana Taran, Yen-Shen Lu |
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Rok vydání: | 2019 |
Předmět: |
Oncology
Cancer Research medicine.medical_specialty Kinase business.industry Advanced breast Endocrine therapy Cancer Ribociclib medicine.disease 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine Gene expression medicine business 030215 immunology |
Zdroj: | Journal of Clinical Oncology. 37:1018-1018 |
ISSN: | 1527-7755 0732-183X |
DOI: | 10.1200/jco.2019.37.15_suppl.1018 |
Popis: | 1018 Background: The Phase III MONALEESA-7 study (NCT02278120) is the first dedicated trial of endocrine therapy (ET) ± a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in premenopausal patients (pts) with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) ABC. The study demonstrated that the addition of ribociclib (RIB) to a nonsteroidal aromatase inhibitor (NSAI) or tamoxifen (TAM) + goserelin (GOS) significantly extended progression-free survival (PFS; hazard ratio [HR] 0.55; Tripathy D, et al. Lancet Oncol. 2018). Here we present a gene expression analysis of baseline tumor mRNA from MONALEESA-7. Methods: Premenopausal pts with HR+/HER2− ABC were treated with RIB or placebo (PBO) + GOS with either an NSAI (letrozole or anastrozole) or TAM. Baseline archival tumor samples from 360 of 672 intent-to-treat (ITT) pts were evaluated for gene expression (RIB n = 185; PBO n = 175) using a customized NanoString nCounter® GX 800-gene panel containing relevant breast cancer, CDK, and proliferation pathway–related genes. Pt subgroups were classified as having low or high mRNA expression using median expression as the cutoff. Results: PFS benefit in the biomarker-assessed group was similar to that in the ITT population. A trend toward a more pronounced PFS benefit with RIB was observed in pts with high vs low expression of CCND1 (HR 0.38 vs 0.67, respectively), IGF1R (HR 0.33 vs 0.77), and ERBB3 (HR 0.33 vs 0.76). The PFS benefit seen with RIB also trended to be greater in pts with low vs high expression of CCNE1 (HR 0.38 vs 0.65, respectively) and MYC (HR 0.37 vs 0.69). The PFS benefit with RIB was similar in pts with high vs low expression of FGFR1 (HR 0.45 vs 0.61, respectively), ESR1 (HR 0.57 vs 0.57), and tumor proliferation genes, such as MKI67 (HR 0.50 vs 0.51). Conclusions: This is the first gene expression analysis of a large set of premenopausal pts with ABC. The benefit with RIB was generally consistent across gene expression subgroups, although the magnitude varied in certain subsets. This analysis suggests that there may be unique resistance mechanisms to ET ± CDK4/6 inhibitors in premenopausal pts with ABC. Clinical trial information: NCT02278120. |
Databáze: | OpenAIRE |
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