Objectives

Neuregulin-1 (NRG1) fusions may drive oncogenesis via constitutive activation of ErbB signaling. Hence, NRG1 fusion-driven tumors may be susceptible to ErbB-targeted therapy. Afatinib (irreversible pan-ErbB inhibitor) has demonstrated activity in individual patients with NRG1 fusion-positive solid tumors. This study collected real-world data on demographics, clinical characteristics, and clinical outcomes in this patient population.

Materials and Methods

In this retrospective, multicenter, non-comparative cohort study, physicians in the US-based Cardinal Health Oncology Provider Extended Network collected data from medical records of patients with NRG1 fusion-positive solid tumors who received afatinib (afatinib cohort) or other systemic therapies (non-afatinib cohort) in any therapy line. Objectives included demographics, clinical characteristics, and outcomes (overall response rate [ORR], progression-free survival [PFS], and overall survival [OS]).

Results

Patients (N = 110) with a variety of solid tumor types were included; 72 received afatinib, 38 other therapies. In the afatinib cohort, 70.8 % of patients received afatinib as second-line treatment and Eastern Cooperative Oncology Group performance status (ECOG PS) was 2–4 in 69.4 % at baseline. In the non-afatinib cohort, 94.7 % of patients received systemic therapy as first-line treatment and ECOG PS was 2–4 in 31.6 % at baseline. In the afatinib cohort, ORR was 37.5 % overall (43.8 % when received as first-line therapy); median PFS and OS were 5.5 and 7.2 months, respectively. In the non-afatinib cohort, ORR was 76.3 %; median PFS and OS were 12.9 and 22.6 months, respectively.

Conclusion

This study provides real-world data on the characteristics of patients with NRG1 fusion-positive solid tumors treated with afatinib or other therapies; durable responses were observed in both groups. However, there were imbalances between the cohorts, and the study was not designed to compare outcomes. Further prospective/retrospective trials are required.

中文翻译：

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携带 NRG1 基因融合的实体瘤患者使用阿法替尼相关的真实世界结果

目标

Neuregulin-1 ( NRG1 ) 融合可能通过 ErbB 信号传导的组成型激活来驱动肿瘤发生。因此，NRG1融合驱动的肿瘤可能对 ErbB 靶向治疗敏感。阿法替尼（不可逆泛 ErbB 抑制剂）已在NRG1融合阳性实体瘤个体患者中表现出活性。这项研究收集了该患者群体的人口统计、临床特征和临床结果的真实数据。

材料和方法

在这项回顾性、多中心、非比较队列研究中，美国康德乐肿瘤学提供者扩展网络的医生从接受阿法替尼（阿法替尼队列）或其他全身治疗的NRG1融合阳性实体瘤患者的医疗记录中收集了数据。任何治疗线中的非阿法替尼队列）。目标包括人口统计学、临床特征和结果（总体缓解率 [ORR]、无进展生存期 [PFS] 和总生存期 [OS]）。

结果

包括患有多种实体瘤类型的患者（N = 110）；72 人接受阿法替尼治疗，38 人接受其他疗法。在阿法替尼队列中，70.8% 的患者接受阿法替尼作为二线治疗，东部肿瘤合作组 (ECOG PS) 基线时 69.4% 的患者体能状态 (ECOG PS) 为 2-4。在非阿法替尼队列中，94.7% 的患者接受全身治疗作为一线治疗，基线时 31.6% 的 ECOG PS 为 2-4。在阿法替尼队列中，总体 ORR 为 37.5%（作为一线治疗时为 43.8%）；中位 PFS 和 OS 分别为 5.5 个月和 7.2 个月。在非阿法替尼队列中，ORR 为 76.3%；中位 PFS 和 OS 分别为 12.9 个月和 22.6 个月。

结论

这项研究提供了接受阿法替尼或其他疗法治疗的NRG1融合阳性实体瘤患者特征的真实世界数据；两组均观察到持久的反应。然而，队列之间存在不平衡，并且该研究并不是为了比较结果而设计的。需要进一步的前瞻性/回顾性试验。