ASCO发布HER2阳性乳腺癌靶向治疗指南

《临床肿瘤学杂志》（Journal of Clinical Oncology）5月5日在线发表了ASCO指南，指南内容涉及晚期HER2阳性乳腺癌患者管理中靶向药物的使用顺序以及脑转移的管理。

美国德克萨斯大学M.D.安德森癌症中心的Sharon H. Giordano博士及其同事在描述这份关于全身性治疗的指南时写道，临床医生应该建议患者一线治疗采用以HER2靶向药物为基础的联合治疗，仅除外经过特别挑选的雌激素受体阳性或孕激素受体阳性的HER2阳性患者；对于这类患者，临床医生可以只采用内分泌治疗（J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0948]）。

晚期疾病的一线治疗建议采用曲妥珠单抗+帕妥珠单抗+一种紫杉类药物的联合治疗。如果患者的乳腺癌在一线HER靶向治疗过程中发生进展，那么二线治疗建议采用曲妥珠单抗emtansine。

对于三线治疗，临床医生应考虑采用其他HER2靶向药物的联合治疗或曲妥珠单抗emtansine（如果之前没有使用过）和帕妥珠单抗（如果之前没有使用过）。

对于伴有临床充血性心力衰竭或左室射血分数明显下降的患者，HER2靶向治疗则应根据个体患者的具体情况进行评估。

指南建议化疗至少持续4~6个月，但是当疾病进展或出现了不可接受的毒性时可以停止治疗。

第二份ASCO指南则针对HER2阳性晚期乳腺癌患者的脑转移管理提出了推荐意见。美国佛罗里达大学奥兰多健康癌症中心的Naren Ramakrishna博士及其同事写道，多达一半的HER2阳性转移性乳腺癌患者都会随时间的推移出现脑转移（J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0955]）。

对于生存预后较好且只有一处脑转移的患者，治疗选择包括手术结合术后放疗、立体定向放射手术、全脑放疗和分次立体定向放疗，具体取决于转移瘤的大小、可切除性和症状。治疗后，建议每2~4个月进行一次影像学检查以监测局部和远处脑转移。

对于生存预后较好且转移范围有限（2~4处）的患者，治疗选择包括手术切除较大的症状性病灶加术后放疗；针对其他较小病灶的立体定向放射手术；全脑放疗和/或立体定向放射手术结合其他病灶的分次立体定向放疗，具体取决于肿瘤的可切除性和症状。

对于弥漫性疾病或广泛转移但预后相对较好的患者，以及脑内症状性软脑膜转移的患者，可以采用全脑放疗。

对于预后较差的患者，指南建议采用全脑放疗、最佳的支持性治疗、参与临床试验和/或姑息治疗。

Ramakrishna博士及其同事称，对于没有脑转移病史或与脑转移相关的症状或者其他任何症状的患者，不建议常规采用磁共振成像（MRI）进行监测。不过，如果患者出现了任何神经系统症状，临床医生则应降低诊断性大脑MRI检查的使用门槛。

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By: REBECCA KERN, Oncology Practice Digital Network

MAY. 9, 2014

FROM THE JOURNAL OF CLINICAL ONCOLOGY

ASCO guidelines addressing the order of targeted agents in the management of patients with advanced HER2-positive breast cancer, and on the management of brain metastases, were published online May 5 in the Journal of Clinical Oncology.

Clinicians should recommend HER2-targeted therapy–based combinations for first-line treatment, except for highly selected patients with estrogen receptor–positive or progesterone receptor–positive and HER2-positive disease, for whom clinicians may use endocrine therapy alone, wrote Dr. Sharon H. Giordano and her colleagues in describing the guideline for systemic treatment (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0948]).

A combination of trastuzumab, pertuzumab, and a taxane is recommended for first-line treatment of advanced disease. If a patient’s breast cancer has progressed during first-line HER2-targeted therapy, trastuzumab emtansine is recommended as a second-line therapy, said Dr. Giordano, of the University of Texas M.D. Anderson Cancer Center, Houston, and her colleagues.

As a third-line treatment, clinicians should prescribe other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and pertuzumab (if not previously administered).

HER2-targeted therapy for those with clinical congestive heart failure or significantly compromised left-ventricular ejection fraction, should be evaluated on a case-by-case basis.

The guideline recommends chemotherapy for at least 4-6 months, but treatment can continue until time of progression or unacceptable toxicities.

The second ASCO guideline provides recommendations for management of brain metastases in patients with HER2-positive advanced breast cancer, which up to half of patients with HER2-positive metastatic breast cancer will experience over time, wrote Dr. Naren Ramakrishna, of the University of Florida Health Cancer Center at Orlando Health, and his colleagues (J. Clin. Oncol. 2014 May 5 [doi: 10.1200/JCO.2013.54.0955]).

For patients with a favorable prognosis for survival and a single brain metastasis, treatment options include surgery with postoperative radiation, stereotactic radiosurgery, whole-brain radiotherapy, and fractionated stereotactic radiotherapy, depending on metastasis size, resectability, and symptoms. After treatment, serial imaging every 2-4 months may be used to monitor for local and distant brain failure.

For patients with a favorable prognosis for survival and limited (two to four) metastases, treatment options include resection for a large symptomatic lesion(s) plus postoperative radiotherapy; stereotactic radiosurgery for additional smaller lesions; and a combination of whole-brain radiotherapy and/or stereotactic radiosurgery and fractionated stereotactic radiotherapy for other lesions, depending on resectability and symptoms.

For patients with diffuse disease or extensive metastases and a more favorable prognosis, and those with symptomatic leptomeningeal metastasis in the brain, whole-brain radiation therapy may be offered.

For patients with a poor prognosis, the guideline recommends whole-brain radiotherapy, best supportive care, clinical trial enrollment, and/or palliative care, Dr. Ramakrishna and his colleagues said.

Routine surveillance with magnetic resonance imaging is not recommended in patients without a history of or symptoms related to brain metastases or symptoms. However, clinicians should have a low threshold for diagnostic brain MRI testing in the setting of any neurologic symptoms, they said.