晚期胃食管腺癌中使用多种基于曲妥珠单抗的化疗方案的临床试验的外部有效性：来自AGAMENON-SEOM注册研究的数据
External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry.
作者信息
Jimenez-Fonseca Paula, Carmona-Bayonas Alberto, Martinez-Torron Alba, Alsina Maria, Custodio Ana, Serra Olbia, Cacho Lavin Diego, Limón María Luisa, Sauri Tamara, López Flora, Visa Laura, Granja Mónica, Martínez Lago Nieves, Arrazubi Virginia, Vidal Tocino Rosario, Hernandez Raquel, Aguado Gema, Cano Juana María, Martín Carnicero Alfonso, Mangas Monserrat, Pimentel Paola, Fernández Montes Ana, Macias Declara Ismael, Longo Federico, Ramchandani Avinash, Martín Richard Marta, Hurtado Alicia, Azkarate Aitor, Hernández Pérez Carolina, Serrano Raquel, Gallego Javier
机构信息
Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain.
Medical Oncology Department, Hospital Universitario Morales Meseguer, Calle Marqués de los Vélez, s/n, Murcia, 30007, Spain.
出版信息
Ther Adv Med Oncol. 2021 Jun 17;13:17588359211019672. doi: 10.1177/17588359211019672. eCollection 2021.
BACKGROUND
Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity.
METHODS
594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab.
RESULTS
The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) ToGA regimens (7.5, 6.4-8.5), < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) intestinal-type tumors (HR 0.76, 0.54-1.06).
CONCLUSION
We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.
背景
基于ToGA试验，曲妥珠单抗联合顺铂和氟嘧啶（卡培他滨或5-氟尿嘧啶，即XP/FP方案）是晚期HER2阳性胃癌患者的标准一线治疗方案。尽管缺乏III期试验，但许多临床医生将曲妥珠单抗与其他方案联合使用。一项荟萃分析表明，用奥沙利铂替代顺铂可能会带来更高的疗效和更低的毒性。
方法
从AGAMENON-SEOM注册中心招募了594例HER2阳性胃食管腺癌患者。目的是评估化疗联合曲妥珠单抗临床试验的外部有效性。
结果
至少5%的患者使用的方案为XP方案（27%）、奥沙利铂联合卡培他滨（CAPOX方案，26%）、奥沙利铂联合5-氟尿嘧啶（FOLFOX方案，14%）、FP方案（14%）、含蒽环类药物/多西他赛的三联方案（7%）以及卡铂-氟尿嘧啶方案（5%）。FOLFOX方案组曲妥珠单抗的中位暴露时间长于ToGA方案组（11.4个月，95%CI：9.1 - 21.0）对比ToGA方案组（7.5个月，6.4 - 8.5个月），P<0.001。HER2免疫组化（IHC）3+癌症患者的缓解率高于IHC 2+/荧光原位杂交（FISH）+患者，比值比为1.97（95%CI：1.25 - 3.09）。CAPOX - 曲妥珠单抗方案取得的结果与ToGA方案相当。FOLFOX - 曲妥珠单抗方案在总生存期（OS）方面优于ToGA方案，在IHC 2+/FISH+肿瘤中（风险比[HR]0.47，0.24 - 0.92）较IHC 3+肿瘤（HR 0.69，0.49 - 0.96）效果更显著；在弥漫型肿瘤（HR 0.37，0.20 - 0.69）对比肠型肿瘤（HR 0.76，0.54 - 1.06）中也是如此。
结论
我们更新了曲妥珠单抗在胃癌一线治疗中临床试验的外部有效性。我们的数据证实了ToGA方案和CAPOX - 曲妥珠单抗方案在临床实践中的疗效相当，并指出FOLFOX - 曲妥珠单抗方案可能有益，但这取决于对曲妥珠单抗通常不太敏感的亚型，有待在临床试验中得到证实。
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