Everolimus plus Exemestane for Hormone Receptor-Positive Advanced Breast Cancer: A PAM50 Intrinsic Subtype Analysis of BOLERO-2

The oncologist

article

Aleix Prat¹  Barbara Adamo¹  Gabriel N. Hortobagyi³  José Baselga⁴  Eva Ciruelos⁵  Jan Christoph Brase⁶  Yuan Cheng⁶  Paolo Nuciforo⁷  Laia Paré¹  Tomás Pascual¹  Débora Martínez¹  Patricia Galván¹  Maria Vidal¹ 

[1] Hospital Clínic de Barcelona;Translational Genomics and Targeted Therapeutics in Solid Tumors Group;The University of Texas MD Anderson Cancer Center;Memorial Sloan Kettering Cancer Center;University Hospital 12 de Octubre;Novartis Pharma AG;Vall d'Hebron Institute of Oncology

关键词: Everolimus;    Exemestane;    Mammalian target of rapamycin;    Advanced breast cancer;    Intrinsic subtype;   

DOI  :  10.1634/theoncologist.2018-0407

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background The prognostic and predictive value of the two nonluminal (human epidermal growth factor receptor 2 [HER2]-enriched and basal-like) subtypes within advanced hormone receptor-positive (HR+) breast cancer is currently unknown. Materials and Methods This study retrospectively analyzed 261 tumors (80.7% primary; 19.3% metastatic) from the BOLERO-2 study; BOLERO-2 randomized 724 patients with advanced HR+/HER2-negative breast cancer to everolimus plus exemestane or placebo plus exemestane. Tumors were classified using a PAM50 subtype predictor. Multivariable Cox regression analyses tested the independent prognostic significance of PAM50, and associations between PAM50 subtypes and treatment upon progression-free survival (PFS) were evaluated. Results Subtype distribution was 46.7% luminal A ( n = 122), 21.5% HER2-enriched ( n = 56), 15.7% luminal B ( n = 41), 14.2% normal-like ( n = 37), and 1.9% basal-like ( n = 5); HER2-enriched subtypes were more common in metastatic versus primary tumors (32.0% vs. 18.7%; p = .038). Median PFS differences between luminal and nonluminal (6.7 vs. 5.2 months; adjusted hazard ratio, 0.66; 95% confidence interval [CI], 0.47–0.94; p = .020) and HER2-enriched and non-HER2-enriched subtypes (5.2 vs. 6.2 months; adjusted hazard ratio, 1.53; 95% CI, 1.07–2.19; p = .019) were significant. Everolimus plus exemestane significantly improved median PFS versus placebo plus exemestane among patients with HER2-enriched tumors (5.8 vs. 4.1 months; adjusted hazard ratio, 0.49; 95% CI, 0.26–0.90; p = .034); however, the association between HER2-enriched tumors and everolimus benefit was nonsignificant ( p = .433). Conclusion The HER2-enriched subtype was identified in a substantial proportion of advanced HR+/HER2-negative breast tumors, and was a consistent biomarker of poor prognosis. Tailored therapies are therefore needed for HER2-enriched tumors in the advanced HR+/HER2-negative breast cancer setting. Implications for Practice Using 261 tumor samples from the BOLERO-2 phase III clinical trial, this study shows that a substantial proportion (20%–30%) of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancers do not have a luminal A or B gene expression profile. This group of patients with nonluminal disease has a poor survival outcome regardless of the addition of everolimus to exemestane. This is the second study that confirms the prognostic value of this biomarker. Overall, these findings indicate a necessity to design novel clinical trials targeting nonluminal disease within HR+/HER2-negative breast cancer.

【 授权许可】

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