小柯机器人

法国巴黎萨克雷大学Fabrice Andre等研究人员发现，基因组学可为转移性乳腺癌患者选择治疗方法。这一研究成果于2022年9月7日在线发表在国际学术期刊《自然》上。

在SAFIR02-BREAST试验中，共有1462名HER2非高表达的转移性乳腺癌患者被邀请接受基因组分析。其中238名患者被随机纳入两项试验（编号：NCT02299999和NCT03386162），比较维持治疗5和与基因组改变相匹配的靶向治疗的疗效。当根据ESMO分子靶点临床可操作性量表（ESCAT）将基因组改变分为I/II级时，与基因组学相匹配的靶向治疗可改善无进展生存期（调整后的危险比（HR）：0.41，90%置信区间（CI）：0.27-0.61，P＜0.001），但当使用ESCAT未选择改变时，则无改善（调整后HR：0.77，95%CI：0.56-1.06，P＝0.109）。对于出现ESCAT改变超过I/II级的患者，在靶向治疗组中没有观察到无进展生存期的改善（未经调整的HR：1.15，95%CI：0.76-1.75）。有种系BRCA1/2突变的患者（n=49）从奥拉帕利中获得了高收益（gBRCA1：HR=0.36，90%CI：0.14-0.89；gBRCA2：HR=0.37，90%CI：0.17-0.78）。这项试验提供的证据表明，在转移性乳腺癌患者中，由基因组学主导的治疗决策应该由靶点可操作的框架驱动。

据悉，癌症的发展部分是由基因组改变驱动的。癌症的基因组特征显示了患者之间在驱动因素改变方面的异质性，导致了这样一个概念，即对癌症患者进行基因组分析可以选择有效的治疗方法。尽管DNA测序已经在实践中得到实施，但仍不清楚如何使用其结果。

附：英文原文

Title: Genomics to select treatment for patients with metastatic breast cancer

Author: Andre, Fabrice, Filleron, Thomas, Kamal, Maud, Mosele, Fernanda, Arnedos, Monica, Dalenc, Florence, Sablin, Marie-Paule, Campone, Mario, Bonnefoi, Herv, Lefeuvre-Plesse, Claudia, Jacot, William, Coussy, Florence, Ferrero, Jean-Marc, Emile, George, Mouret-Reynier, Marie-Ange, Thery, Jean-Christophe, Isambert, Nicolas, Mege, Alice, Barthelemy, Philippe, You, Benoit, Hajjaji, Nawale, Lacroix, Ludovic, Rouleau, Etienne, Tran-Dien, Alicia, Boyault, Sandrine, Attignon, Valery, Gestraud, Pierre, Servant, Nicolas, Le Tourneau, Christophe, Cherif, Linda Larbi, Soubeyran, Isabelle, Montemurro, Filippo, Morel, Alain, Lusque, Amelie, Jimenez, Marta, Jacquet, Alexandra, Gonalves, Anthony, Bachelot, Thomas, Bieche, Ivan

Issue&Volume: 2022-09-07

Abstract: Cancer progression is driven in part by genomic alterations1. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations2, leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies3,4. Although DNA sequencing has been implemented in practice, it remains unclear how to use its results. A total of 1,462patients with HER2-non-overexpressing metastatic breast cancer were enroled to receive genomic profiling in the SAFIR02-BREAST trial. Two hundred and thirty-eight of these patients were randomized in two trials (nos. NCT02299999 and NCT03386162) comparing the efficacy of maintenance treatment5 with a targeted therapy matched to genomic alteration. Targeted therapies matched to genomics improves progression-free survival when genomic alterations are classified as levelI/II according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)6 (adjusted hazards ratio (HR): 0.41, 90% confidence interval (CI): 0.27–0.61, P<0.001), but not when alterations are unselected using ESCAT (adjusted HR: 0.77, 95% CI: 0.56–1.06, P=0.109). No improvement in progression-free survival was observed in the targeted therapies arm (unadjusted HR: 1.15, 95% CI: 0.76–1.75) for patients presenting with ESCAT alteration beyond levelI/II. Patients with germline BRCA1/2 mutations (n=49) derived high benefit from olaparib (gBRCA1: HR=0.36, 90% CI: 0.14–0.89; gBRCA2: HR=0.37, 90% CI: 0.17–0.78). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic breast cancer.

DOI: 10.1038/s41586-022-05068-3

Source: https://www.nature.com/articles/s41586-022-05068-3

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