A new era of improving progression-free survival with dual blockade in postmenopausal HR+, HER2- advanced breast cancer

被引:17
|
作者
Jerusalem, Guy [1 ,2 ]
Bachelot, Thomas [3 ]
Barrios, Carlos [4 ]
Neven, Patrick [5 ]
Di Leo, Angelo [6 ]
Janni, Wolfgang [7 ]
de Boer, Richard [8 ]
机构
[1] Univ Sart Tilman Liege, Ctr Hosp, B-4000 Liege, Belgium
[2] Univ Liege, B-4000 Liege, Belgium
[3] INSERM, U1052 CNKS 5286, Ctr Leon Berard, Ctr Rech Cancerol Lyon, F-69373 Lyon 08, France
[4] Pontificia Univ Catolica Rio Grande do Sul, Sch Med, BR-90570080 Porto Alegre, RS, Brazil
[5] Univ Hosp, Leuven, Belgium
[6] Hosp Prato, Ist Toscani Tumori, Prato, Italy
[7] Univ Ulm, Womens Hosp, D-89075 Ulm, Germany
[8] Royal Melbourne Hosp, Parkville 3050, Australia
关键词
Endocrine therapy; Everolimus; Hormone receptor-positive advanced breast cancer; mTOR inhibitor; Overall survival; Progression-free survival; EVEROLIMUS PLUS EXEMESTANE; INTERNATIONAL CONSENSUS GUIDELINES; PLACEBO-CONTROLLED TRIAL; RANDOMIZED PHASE-II; DOUBLE-BLIND; AROMATASE INHIBITORS; RAPAMYCIN PATHWAY; ENDOCRINE THERAPY; MAMMALIAN TARGET; WOMEN;
D O I
10.1016/j.ctrv.2014.12.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Disease progression despite existing endocrine therapies remains a major challenge to the effective management of hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2(-)), advanced breast cancer. Recent advances in elucidating the molecular mechanisms of disease progression have identified the existence of adaptive "cross-talk" between the estrogen receptor (ER) and various growth factor receptor and intracellular signaling pathways, allowing breast cancer cells to escape the inhibitory effects of endocrine therapy. These findings provide the clinical rationale for enhancing or extending endocrine sensitivity by combining endocrine therapy with a targeted agent against a compensatory pathway. In BOLERO-2, adding the mTOR inhibitor everolimus to endocrine therapy significantly improved progression-free survival (PFS) in patients with HR+ advanced breast cancer previously treated with nonsteroidal aromatase inhibitor therapy. Notably, PFS benefits were comparable in subgroup analyses of first- and later-line settings. These results contrast with those of the large first-line HORIZON study, wherein adding the mTOR inhibitor temsirolimus to endocrine therapy did not improve PFS. Therefore, it is unclear whether a targeted agent should only be combined with endocrine therapy to restore endocrine sensitivity or whether it may also prevent or delay resistance in hormone-sensitive advanced breast cancer. Numerous additional targeted agents are currently being evaluated in combination with endocrine therapies, including PI3K, cyclin-dependent kinase 4/6, SRC, and histone deacetylase inhibitors. Appropriate patient selection based on prior treatment history will become increasingly important in maximizing the incremental benefit derived from these new agents combined with existing endocrine therapies in HR+ advanced breast cancer. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:94 / 104
页数:11
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