背景:克唑替尼已在许多国家被批准用于治疗晚期ROS1重排的非小细胞肺癌(NSCLC)患者。Entrectinib是一种ROS1抑制剂,旨在有效穿透并保留在中枢神经系统(CNS)中,并被推荐作为一线治疗。很少有报告准确描述了在后来的情况下ROS1融合患者的序贯克唑替尼和恩曲替尼。
方法:一名56岁有偶尔吸烟史的男子因咳嗽到我院就诊,痰,呼吸急促.
方法:他被诊断为右肺腺癌(T4N2M1a,IV期)图像和组织学检查后,无EGFR或ALK融合突变。
方法:他之前接受了三行治疗,包括化疗,纳武单抗单药治疗,紫杉醇加安洛替尼,无进展生存期(PFS)为5、2和11.5个月,分别。然后病人开始出现头痛和头晕,脑磁共振成像显示多发脑转移。来自颈部淋巴结的活检的下一代测序(NGS)鉴定为EZR-ROS1(1.25%丰度)。克唑替尼(每日250毫克)加贝伐单抗2个月后,所有肺部和脑部病变都减少了,但是发现了一个小的肝脏病变。随着治疗又持续了4个月,肝脏病变继续生长,而其他病变保持减少或稳定状态。外周血NGS分析发现EZR-ROS1融合消失和一个新的NTRK2突变(c.5C>T,p.Ser2Leu,0.34%丰度)无其他可靶向分子改变。他接受了entrectinib(每天600mg)加贝伐单抗,并获得部分缓解。经过7个月的治疗,检查显示脑部病变进展。
结果:患者从克唑替尼和恩曲替尼序贯治疗后总PFS为13个月。
结论:酪氨酸激酶抑制剂序贯治疗克唑替布,然后服用恩列替尼,ROS1重排的NSCLC伴中枢神经系统转移。该报告对指导克唑替尼耐药后的治疗决策具有潜在意义。
BACKGROUND: Crizotinib has been approved in many countries for the treatment of patients with advanced ROS1-rearranged non-small cell lung cancers (NSCLC). Entrectinib is a ROS1 inhibitor that has been designed to effectively penetrate and remain in the central nervous system (CNS) and has been recommended as first-line therapy. Few
reports have precisely described sequential crizotinb followed by entrectinib in patients with ROS1 fusion in later settings.
METHODS: A 56-year-old man with a history of occasional smoking visited our hospital with cough, sputum, and shortness of breath.
METHODS: He was diagnosed with right lung adenocarcinoma (T4N2M1a, stage IV) after image and histological examination, without EGFR or ALK fusion mutation.
METHODS: He received three prior lines of therapies, including chemotherapy, nivolumab monotherapy, and paclitaxel plus anlotinib, with progression-free survival (PFS) of 5, 2, and 11.5 months, respectively. Then the patient began to have headaches and dizziness, and brain magnetic resonance imaging showed multiple brain metastases. Next-generation sequencing (NGS) of the biopsy from neck lymph node identified EZR-ROS1 (1.25% abundance). After 2 months of crizotinib (250 mg daily) plus bevacizumab, all pulmonary and brain lesions decreased, but a small liver lesion was discovered. As treatment went on for another 4 months, the liver lesion continued to grow while other lesions kept decreased or stable state. NGS analysis on the peripheral blood found the disappearance of EZR-ROS1 fusion and a new NTRK2 mutation (c.5C>T, p.Ser2Leu, 0.34% abundance) without other targetable molecular alteration. He received entrectinib (600 mg daily) plus bevacizumab and achieved a partial response. After 7 months of therapy, examination revealed progression of brain lesions.
RESULTS: The patient had a total PFS of 13 months from sequential crizotinib and entrectinib therapy.
CONCLUSIONS: A ROS1-rearranged NSCLC with CNS metastases responded to sequential tyrosine kinase inhibitors treatment of crizotinb followed by entrectinib. This report has potential implications in guiding decisions for the treatment after crizotinib resistance.