Background/Objectives: 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.Methods: Patients from the AGAMENON-SEOM registry who initiated 1L polychemotherapy for advanced G/GEJa (2015–2019) in Spain were included.Results: 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-rankp< 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];p= 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.Conclusions: 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.
背景/目的：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/胃食管结合部腺癌（晚期G/GEJa）患者生存结局较差，且目前缺乏有效的靶向治疗。本研究在免疫治疗时代之前开展，旨在描述西班牙启动一线（1L）治疗的晚期G/GEJa患者中HER2阴性及阳性患者的特征与治疗管理，比较其生存差异，并估算符合1L联合化疗条件的HER2阴性患者数量。 方法：纳入西班牙AGAMENON-SEOM登记库中于2015年至2019年间启动1L联合化疗的晚期G/GEJa患者。 结果：共纳入1357例患者（HER2阴性951例[70.1%]；HER2阳性315例[23.2%]；HER2状态不明91例[6.7%]）。多数患者（56.3%）接受了一线治疗；27.6%接受二线治疗；16.1%接受三线治疗。在HER2阳性患者中，92.7%在1L治疗中接受了曲妥珠单抗。研究期间（2015-2019年），FOLFOX与CAPOX方案的使用率逐年上升。与HER2阳性患者相比，HER2阴性患者的无进展生存期（中位数5.92个月[95% CI, 5.59–6.38] vs. 7.37个月[95% CI, 6.55–8.29]；时序检验p<0.0001）和总生存期（中位数10.49个月[95% CI, 9.74–11.05] vs. 13.82个月[95% CI, 12.30–14.74]；校正时间比0.812[95% CI, 0.722–0.913]；p=0.0005）均显著缩短。概率敏感性分析估算，2024年西班牙约有2856例（95% CI, 1619–4134）HER2阴性晚期G/GEJa患者符合1L联合化疗条件。 结论：HER2阳性与阴性患者间的生存差异凸显了在1L治疗中为HER2阴性患者开发靶向疗法的迫切需求。
肿瘤(癌症)患者之家