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对转移性乳腺癌患者选择治疗的基因组学

Fabrice Andre^1,2,3,4, Thomas Filleron⁵, Maud Kamal⁶

¹Department of Medical Oncology, Gustave Roussy, Villejuif, France. fabrice.andre@gustaveroussy.fr.

|September 7, 2022

概括

在转移性乳腺癌中,当向治疗与可操作的基因组改变相匹配时,基因组分析可以改善无进展的存活率 (I/II级). 这一策略为非HER2过度表达瘤患者的有效治疗决策提供指导.

科学领域:

癌症学
基因组学
临床试验

背景情况:

基因组变化驱动癌症的进展,并表现出显著的患者间异质性.
基因组分析可以为向治疗选择提供信息,但其临床效用需要澄清.
在SAFIR02- BREAST试验中,研究了HER2- 不过度表达的转移性乳腺癌的基因组分析.

研究的目的:

对转移性乳腺癌患者的基因组变异进行匹配的向治疗的有效性进行评估.
确定目标可操作性框架是否与未选择的基因组改变相比改善治疗结果.

主要方法:

有1462名非HER2过度表达的转移性乳腺癌患者接受了基因组分析.
238名患者被随机分配到与基因组变化相匹配的向治疗中.
基因组变化使用ESMO分子标临床可行性量表 (ESCAT) 进行分类.

主要成果:

针对ESCAT I/ II水平的向治疗显著改善了无进展的存活率 (调整后的HR为0. 41).
对于未选择的变化或超出ESCAT I/ II的变化,没有观察到无进展生存的显著改善.
患有生殖系BRCA1/ 2突变的患者从olaparib中获得了显著的益处 (gBRCA1 HR: 0. 36; gBRCA2 HR: 0. 37).

结论:

由目标可操作性框架 (ESCAT I/II级) 引导的基因组分析可以改善转移性乳腺癌的无进展生存率.
转移性乳腺癌的治疗决定应由可操作的基因组变化决定.
特定的基因组变异,如生殖系BRCA1/ 2突变,可以确定受益于特定向治疗的患者 (例如,olaparib).

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