The growth of genotype-directed targeted therapies, such as inhibitors of the epidermal growth factor receptor (EGFR), has revolutionized treatment for some patients with oncogene-addicted lung cancer. However, as systemic control for these patients has improved, brain metastases remain an important source of morbidity and mortality. Traditional treatment for brain metastases has been radiotherapy, either whole-brain radiation or stereotactic radiosurgery. The growing availability of drugs that can cross the blood-brain barrier and have activity in the central nervous system (CNS) has led to many studies investigating whether targeted therapy can be used in combination with or in lieu of radiation. In this review, we summarize the key literature about the incidence and nature of EGFR-mutant brain metastases (EGFR BMs), the data about the activity of EGFR inhibitors in the CNS, and whether they can be used as front-line therapy for brain metastases. Although initial use of tyrosine kinase inhibitors for EGFR BMs can often be an effective treatment strategy, multidisciplinary evaluation is critical, and prospective studies are needed to clarify which patients may benefit from early radiotherapy.
Implications for practice: Management of brain metastases in epidermal growth factor receptor (EGFR) mutant lung cancer is a common clinical problem. The question of whether to start initial therapy with an EGFR inhibitor or radiotherapy (either whole-brain radiotherapy or stereotactic radiosurgery) is controversial. The development of novel EGFR inhibitors with enhanced central nervous system (CNS) penetration is an important advance in the treatment of CNS disease. Multidisciplinary evaluation and evaluation of extracranial disease status are critical to choosing the best treatment option for each patient.
摘要
表皮生长因子受体(EGFR)抑制剂等基因靶向治疗的发展为某些癌基因依赖性肺癌的治疗带来了革命性的变化。然而,尽管这些患者的系统控制已经有所改善,但脑转移仍然是病损和死亡的一个重要原因。放疗包括全脑放疗或立体定向放射手术是脑转移的传统治疗方法。可透过血脑屏障并且作用于中枢神经系统 (CNS)的药物越来越多,因此,许多研究探索了靶向治疗是否可与放疗结合或者替代放疗。在本篇综述中,我们总结了关于EGFR突变脑转移(EGFR BMs)的发病率及其性质的关键文献、关于CNS中EGFR抑制剂活性的数据、以及EGFR抑制剂是否可用作脑转移的一线疗法。尽管初始使用酪氨酸激酶抑制剂治疗EGFR BMs通常是一种有效治疗策略,但多学科评估是关键,未来需要展开前瞻性研究以明确哪些患者可获益于早期放疗。
实践意义:表皮生长因子受体(EGFR)突变肺癌脑转移的治疗是一个常见的临床问题。应当用EGFR抑制剂还是放疗(全脑放疗或立体定向放射手术)作为初始治疗尚存在争议。具有更强中枢神经系统(CNS)渗透力的新型EGFR抑制剂的开发是治疗CNS疾病的一个重要进展。多学科评估和颅外疾病状态评估对于为每位患者选择最佳治疗方案至关重要
Keywords: Brain metastases; Epidermal growth factor receptor mutation; Lung cancer; Radiation therapy; Targeted therapy.
© AlphaMed Press 2018.