神经调节蛋白1(NRG1)融合,激活ErbB信号,是多种肿瘤类型中罕见的致癌驱动因素。阿法替尼是一种泛ErbB家族抑制剂,可能是NRG1融合驱动肿瘤的有效治疗方法。
本报告总结了相关细节,包括肿瘤对治疗的最佳反应,对于6例接受阿法替尼治疗的转移性NRG1融合阳性肿瘤患者。
6例患者包括4名女性和2名男性患者,年龄在34至69岁之间。其中5例为肺癌患者,包括两名浸润性黏液腺癌和三名非黏液腺癌患者。第六例是结直肠癌患者。肺癌患者的NRG1融合伴侣是CD74或SDC4。患有结直肠癌的患者具有新的POMK-NRG1融合和KRAS突变。两名患者接受阿法替尼作为一线或二线治疗,三名患者接受了该药物作为三至五线治疗,1例患者接受阿法替尼作为第15线治疗.阿法替尼的最佳反应是两名患者的病情稳定(与局部治疗联合时持续时间长达16个月),三名患者的部分反应(PR)>18个月。包括27个月后正在进行公关的人。其余患者使用阿法替尼40mg/天的PR为5个月,然后再增加到50毫克/天6个月后。
本报告回顾了以前发表的用阿法替尼治疗的转移性NRG1融合阳性肿瘤,并总结了6例以前未发表的病例。后者包括几个对治疗有长期反应(>18个月),以及首次报道NRG1融合阳性结直肠癌的疗效。这增加了越来越多的证据,表明阿法替尼可以对NRG1融合阳性肿瘤患者有效。
NRG1融合激活ErbB信号传导,并已被确定为多种实体瘤类型的致癌驱动因素。阿法替尼是一种泛ErbB家族抑制剂,被授权用于治疗晚期非小细胞肺癌,可能对NRG1融合驱动的肿瘤有效。本报告总结了6例以前未发表的NRG1融合驱动的癌症患者使用阿法替尼治疗,包括5例转移性肺癌和1例转移性结直肠癌。一些患者在阿法替尼治疗下表现出>18个月的延长反应。该病例系列增加了证据,表明阿法替尼在未满足的医疗需求领域具有潜在作用。
Neuregulin 1 (NRG1) fusions, which activate ErbB signaling, are rare oncogenic drivers in multiple tumor types. Afatinib is a pan-ErbB family inhibitor that may be an effective treatment for NRG1 fusion-driven tumors.
This report summarizes pertinent details, including best tumor response to treatment, for six patients with metastatic NRG1 fusion-positive tumors treated with afatinib.
The six cases include four female and two male patients who ranged in age from 34 to 69 years. Five of the cases are patients with lung cancer, including two patients with invasive mucinous adenocarcinoma and three patients with nonmucinous adenocarcinoma. The sixth
case is a patient with colorectal cancer. NRG1 fusion partners for the patients with lung cancer were either CD74 or SDC4. The patient with colorectal cancer harbored a novel POMK-NRG1 fusion and a KRAS mutation. Two patients received afatinib as first- or second-line therapy, three patients received the drug as third- to fifth-line therapy, and one patient received afatinib as fifteenth-line therapy. Best response with afatinib was stable disease in two patients (duration up to 16 months when combined with local therapies) and partial response (PR) of >18 months in three patients, including one with ongoing PR after 27 months. The remaining patient had a PR of 5 months with afatinib 40 mg/day, then another 6 months after an increase to 50 mg/day.
This report reviews previously published metastatic NRG1 fusion-positive tumors treated with afatinib and summarizes six previously unpublished cases. The latter include several with a prolonged response to treatment (>18 months), as well as the first report of efficacy in NRG1 fusion-positive colorectal cancer. This adds to the growing body of evidence suggesting that afatinib can be effective in patients with NRG1 fusion-positive tumors.
NRG1 fusions activate ErbB signaling and have been identified as oncogenic drivers in multiple solid tumor types. Afatinib is a pan-ErbB family inhibitor authorized for the treatment of advanced non-small cell lung cancer that may be effective in NRG1 fusion-driven tumors. This report summarizes six previously unpublished cases of NRG1 fusion-driven cancers treated with afatinib, including five with metastatic lung cancer and one with metastatic colorectal cancer. Several patients showed a prolonged response of >18 months with afatinib treatment. This
case series adds to the evidence suggesting a potential role for afatinib in this area of unmet medical need.