Jimenez-Fonseca Paula, Carmona-Bayonas Alberto, Álvarez-Cañada Jaime, Storfer-Isser Amy, Martin-Richard Marta, Sauri Tamara, Cano Juana María, Martínez Moreno Elia, Pérez-Wert Pablo, López Javier, Garcia Navalon Francisco, Gómez-González Lucía, Ruiz Martín Maribel, Rupérez Blanco Ana Belén, López-López Flora, Roncancio-Díaz Emilse, Corbacho Belén, Mateo Marta, Anguita-Alonso Paloma, Gallego Plazas Javier
Medical Oncology Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.
Medical Oncology Department, Hospital Universitario Morales Meseguer, Instituto Murciano de Investigación Biosanitaria (IMIB), University of Murcia, 30008 Murcia, Spain.
Cancers (Basel). 2025 Jun 27;17(13):2164. doi: 10.3390/cancers17132164.
: Human epidermal growth factor receptor 2-negative (HER2-negative), locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (advanced G/GEJa) is associated with poor survival outcomes, and there is an unmet need for targeted therapy. This study, conducted in the pre-immunotherapy era, aimed to describe the characteristics and management, and compare the survival, of HER2-negative and HER2-positive patients initiating first-line (1L) treatment for advanced G/GEJa in Spain and estimate the number of HER2-negative patients eligible for 1L polychemotherapy. : Patients from the AGAMENON-SEOM registry who initiated 1L polychemotherapy for advanced G/GEJa (2015-2019) in Spain were included. : In total, 1357 patients were included (951 [70.1%] HER2-negative; 315 [23.2%] HER2-positive; 91 [6.7%] unknown HER2 status). Most patients (56.3%) received one line of therapy; 27.6% received two lines; and 16.1% received three lines. Among HER2-positive patients, 92.7% received trastuzumab as part of 1L treatment. The use of FOLFOX and CAPOX increased over the study period (2015-2019). HER2-negative patients had significantly shorter progression-free survival (median, 5.92 months [95% CI, 5.59-6.38] vs. 7.37 months [95% CI, 6.55-8.29]; log-rank < 0.0001) and overall survival (median, 10.49 months [95% CI, 9.74-11.05] vs. 13.82 months [95% CI, 12.30-14.74]; adjusted time ratio, 0.812 [95% CI, 0.722-0.913]; = 0.0005) than HER2-positive patients. Per probabilistic sensitivity analyses, an estimated 2856 (95% CI, 1619-4134) Spanish patients with HER2-negative advanced G/GEJa were eligible for 1L polychemotherapy in 2024. : The survival difference between HER2-positive and HER2-negative patients underscores the critical need for targeted therapies for HER2-negative patients in the 1L setting.
人表皮生长因子受体2阴性（HER2阴性）的局部晚期或转移性胃/胃食管交界腺癌（晚期G/GEJa）患者生存结局较差，靶向治疗仍存在未满足的需求。本研究在免疫治疗时代之前进行，旨在描述HER2阴性和HER2阳性的西班牙晚期G/GEJa患者一线（1L）治疗的特征与管理情况，并比较其生存率，同时估计符合1L多药化疗条件的HER2阴性患者数量。纳入西班牙AGAMENON - SEOM注册中心2015 - 2019年开始接受晚期G/GEJa一线多药化疗的患者。共纳入1357例患者（951例[70.1%]HER2阴性；315例[23.2%]HER2阳性；91例[6.7%]HER2状态未知）。大多数患者（56.3%）接受了一线治疗；27.6%接受了二线治疗；16.1%接受了三线治疗。在HER2阳性患者中，92.7%接受曲妥珠单抗作为1L治疗的一部分。在研究期间（2015 - 2019年），FOLFOX和CAPOX方案的使用有所增加。HER2阴性患者的无进展生存期显著短于HER2阳性患者（中位数分别为5.92个月[95%CI，5.59 - 6.38]和7.37个月[95%CI，6.55 - 8.29]；对数秩检验<0.0001），总生存期也显著较短（中位数分别为10.49个月[95%CI，9.74 - 11.05]和13.82个月[95%CI，12.30 - 14.74]；校正时间比为0.812[95%CI，0.722 - 0.913]；P = 0.0005）。根据概率敏感性分析，预计2024年西班牙有2856例（95%CI，1619 - 4134）HER2阴性晚期G/GEJa患者符合1L多药化疗条件。HER2阳性和HER2阴性患者之间的生存差异凸显了在1L治疗中为HER2阴性患者提供靶向治疗的迫切需求。
