晚期乳腺癌循环肿瘤细胞非劣效足矣？ / 开普饭

　　对于激素受体阳性且HER2阴性晚期乳腺癌，一线治疗应该选择化疗还是内分泌治疗，通常由临床医师根据不良预后相关临床特征决定。对于此类患者，每7.5毫升外周血液循环肿瘤细胞（CTC）计数≥5个与<5个相比，总生存和无进展生存显著较差，也有助于决定一线治疗应该选择化疗还是内分泌治疗。

　　2020年11月5日，《美国医学会杂志》肿瘤学分册在线发表法国居里研究院、巴黎萨克雷大学、凡尔赛大学、巴黎文理研究大学、癌症生物治疗临床研究中心、索邦大学特农医院、圣路易医院、巴黎大学、蒙彼利埃大学、蒙彼利埃癌症研究中心、蒙彼利埃大学医疗中心、莱昂·贝拉德癌症中心、维克多·雨果医院、保利·卡拉梅特斯癌症研究中心、马赛大学、乔治斯-弗朗索瓦·勒克莱尔癌症中心、法国里维埃拉癌症中心、克劳迪乌斯·雷戈德癌症研究中心、弗朗索瓦·巴克莱斯癌症中心、安托万·拉卡萨涅癌症中心、欧仁·马奎斯癌症中心的法国国家癌症研究所昂贵创新技术支持项目（STIC）CTC研究报告，比较了由临床医师选择或根据CTC选择激素受体阳性且HER2阴性晚期乳腺癌一线治疗方案对患者无进展生存的影响。

NCT01710605 (STIC CTC): Randomized Trial to Evaluate the Medico-economic Interest of Taking Into Account Circulating Tumor Cells (CTC) to Determine the Kind of First Line Treatment for Metastatic, Hormone-receptors Positive, Breast Cancers

　　该多中心非盲随机对照非劣效三期临床研究于2012年2月1日～2016年7月28日从法国17个癌症中心入组年龄≥18岁绝经前或绝经后激素受体阳性且HER2阴性晚期乳腺癌女性755例（年龄30～88岁，中位63岁）按1∶1随机分为两组：

CTC组377例（年龄30～88岁，中位64岁）根据CTC计数接受化疗（如果每7.5毫升外周血液CTC≥5个）或内分泌治疗（如果每7.5毫升外周血液CTC<5个）
对照组378例（年龄31～87岁，中位63岁）由研究者（临床医师）选择一线治疗方案

　　2019年6月～2019年10月进行数据分析。主要终点为研究者评定完成治疗方案患者的无进展生存，预设进展死亡风险比的90%置信区间非劣效上限为1.25。

　　结果，CTC组与对照组相比：

接受化疗患者：138例、103例（37%比27%）
无进展生存期：中位15.5个月比13.9个月（95%置信区间：12.7～17.3、12.2～16.3）
进展死亡风险：低6%（风险比：0.94，90%置信区间：0.81～1.09）达到主要终点

　　因此，该随机临床研究结果表明，对于激素受体阳性且HER2阴性晚期乳腺癌的一线治疗方案，CTC计数可能是一种可靠的生物标志测定方法，有助于临床医师选择化疗或内分泌治疗。

　　对此，美国印第安纳大学西蒙综合癌症中心发表同期评论：评估晚期乳腺癌CTC计数的临床效果非劣效足矣？

JAMA Oncol. 2020 Nov 5. Online ahead of print.

Efficacy of Circulating Tumor Cell Count-Driven vs Clinician-Driven First-line Therapy Choice in Hormone Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: The STIC CTC Randomized Clinical Trial.

Bidard FC, Jacot W, Kiavue N, Dureau S, Kadi A, Brain E, Bachelot T, Bourgeois H, Goncalves A, Ladoire S, Naman H, Dalenc F, Gligorov J, Espié M, Emile G, Ferrero JM, Loirat D, Frank S, Cabel L, Diéras V, Cayrefourcq L, Simondi C, Berger F, Alix-Panabières C, Pierga JY.

Institut Curie, UVSQ and Paris-Saclay University, Saint-Cloud, France; Center of Clinical Investigations in Biotherapies of Cancer, Paris, France; Institut Curie, PSL Research University, Paris, France; Hopital Tenon, Sorbonne Université, Paris, France; Hopital Saint-Louis, Paris, France; Institut Curie, Université de Paris, Paris, France; Institut Curie, Paris, France; Institut du Cancer de Montpellier, Institut de Recherche en Cancérologie de Montpellier, Montpellier University, Montpellier, France; University Medical Center of Montpellier, Montpellier University, Montpellier, France; Centre Léon Bérard, Lyon, France; Victor Hugo Clinic, Le Mans, France; Institut Paoli-Calmettes, CRCM, Aix-Marseille University, Marseille, France; Centre Georges Francois Leclerc, Dijon, France; Centre Azuréen de Cancérologie, Mougins, France; Institut Claudius Regaud, Toulouse, France; Centre Francois Baclesse, Caen, France; Centre Antoine Lacassagne, Nice, France; Centre Eugène Marquis, Rennes, France.

This phase 3 randomized clinical trial assesses the efficacy of a clinician-driven treatment choice vs a circulating tumor cell count-driven choice for first-line treatment among women with hormone receptor-positive, ERBB2-negative metastatic breast cancer.

QUESTION: Can the circulating tumor cell (CTC) count be used as an alternative to the clinical evaluation as the basis for determining the first-line treatment choice (chemotherapy or endocrine therapy) in hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer?

FINDINGS: In this randomized clinical trial that allocated 778 patients to a clinician-driven choice arm or a CTC-driven choice arm, the CTC arm was noninferior for progression-free survival.

MEANING: The CTC count may be a reliable biomarker for choosing between chemotherapy and single-agent endocrine therapy as the first-line treatment in hormone receptor-positive ERBB2-negative metastatic breast cancer.

IMPORTANCE: The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS).

OBJECTIVE: To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment.

INTERVENTIONS: In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), whereas in the control arm, the choice was left to the investigator.

DESIGN, SETTING, AND PARTICIPANTS: In the STIC CTC randomized, open-label, noninferiority phase 3 trial, participants were randomized to a clinician-driven choice of first-line treatment or a CTC count-driven first-line treatment choice. Eligible participants were premenopausal and postmenopausal women 18 years or older diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer. Data were collected at 17 French cancer centers from February 1, 2012, to July 28, 2016, and analyzed June 2019 to October 2019.

MAIN OUTCOME AND MEASURES: The primary end point was the investigator-assessed PFS in the per-protocol population, with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio.

RESULTS: Among the 755 women in the per-protocol population, the median (range) age was 63 (30-88) years [64 (30-88) years for the 377 patients allocated to the CTC arm and 63 (31-87) years for the 378 patients allocated to the standard arm]; 138 (37%) and 103 (27%) received chemotherapy, respectively. Median PFS was 15.5 months (95% CI, 12.7-17.3) in the CTC arm and 13.9 months (95% CI, 12.2-16.3) in the standard arm. The primary end point was met, with a hazard ratio of 0.94 (90% CI, 0.81-1.09).

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that the CTC count may be a reliable biomarker method for guiding the choice between chemotherapy and endocrine therapy as the first-line treatment in hormone receptor-positive, ERBB2-negative metastatic breast cancer.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01710605

PMID: 33151266

DOI: 10.1001/jamaoncol.2020.5660