Assistance Publique Hôpitaux de Paris, Hôpital Tenon and Groupes de recherche clinique Theranoscan and Curamus Sorbonne Université, Paris, France.
Georgetown University Medical Center, Washington, District of Columbia, USA.
Oncologist. 2021 Jan;26(1):7-16. doi: 10.1634/theoncologist.2020-0379. Epub 2020 Sep 23.
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reviews previously published metastatic NRG1 fusion-positive tumors treated with afatinib and summarizes six previously unpublished cases.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 This report summarizes six previously unpublished cases of NRG1 fusion-driven cancers treated with afatinib, including five with metastatic lung cancer and one with metastatic colorectal cancer.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.
神经调节蛋白 1（NRG1）融合物可激活 ErbB 信号通路，是多种肿瘤类型中罕见的致癌驱动因子。阿法替尼是一种泛-ErbB 家族抑制剂，可能是治疗 NRG1 融合驱动肿瘤的有效药物。
本报告总结了 6 例转移性 NRG1 融合阳性肿瘤患者使用阿法替尼治疗的相关详细信息，包括最佳肿瘤缓解情况。
这 6 例患者包括 4 名女性和 2 名男性，年龄 34 岁至 69 岁。其中 5 例为肺癌患者，包括 2 例浸润性黏液腺癌和 3 例非黏液腺癌。第 6 例为结直肠癌患者。肺癌患者的 NRG1 融合伙伴为 CD74 或 SDC4。结直肠癌患者携带新型 POMK-NRG1 融合和 KRAS 突变。2 例患者接受阿法替尼一线或二线治疗，3 例患者接受三线至五线治疗，1 例患者接受阿法替尼十五线治疗。2 例患者的最佳缓解为疾病稳定（联合局部治疗时持续时间长达 16 个月），3 例患者的缓解为部分缓解（PR）>18 个月，其中 1 例 PR 持续 27 个月。另 1 例患者阿法替尼 40 mg/天治疗 5 个月后，增加剂量至 50 mg/天后又缓解 6 个月。
本报告回顾了先前使用阿法替尼治疗的转移性 NRG1 融合阳性肿瘤，并总结了 6 例先前未发表的病例。后者包括一些患者的治疗反应持续时间较长（>18 个月），以及首例 NRG1 融合阳性结直肠癌疗效的报道。这增加了越来越多的证据，表明阿法替尼对 NRG1 融合阳性肿瘤患者可能有效。
NRG1 融合物激活 ErbB 信号通路，已被确定为多种实体肿瘤类型的致癌驱动因子。阿法替尼是一种泛-ErbB 家族抑制剂，已获批准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 例使用阿法替尼治疗的 NRG1 融合驱动癌症患者的情况，包括 5 例转移性肺癌和 1 例转移性结直肠癌。数名患者接受阿法替尼治疗的缓解时间>18 个月。本病例系列为阿法替尼在这一具有未满足医疗需求领域的潜在作用提供了更多证据。
