Is there a preferred platinum and fluoropyrimidine regimen for advanced HER2-negative esophagogastric adenocarcinoma? Insights from 1293 patients in AGAMENON–SEOM registry

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2024年2月15日

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Aranzazu Arias-Martinez,
Eva Martínez de Castro,
Javier Gallego,
Virginia Arrazubi,
Ana Custodio,
Ana Fernández Montes,
Marc Diez,
Raquel Hernandez,
María Luisa Limón,
Juana María Cano,
Rosario Vidal-Tocino,
Ismael Macias,
Laura Visa,
Marta Martin Richard,
Tamara Sauri,
Cinta Hierro,
Mireia Gil,
Paula Cerda,
Elia Martínez Moreno,
Nieves Martínez Lago,
Antonio José Mérida-García,
Lucía Gómez González,
Francisco Javier García Navalón,
Maribel Ruiz Martín,
Gema Marín,
Flora López-López,
Ana Belen Ruperez Blanco,
Alejandro Francisco Fernández,
Paula Jimenez-Fonseca,
Alberto Carmona-Bayonas,
Felipe Alvarez-Manceñido

摘要

Background

The optimal chemotherapy backbone for HER2-negative advanced esophagogastric cancer, either in combination with targeted therapies or as a comparator in clinical trials, is uncertain. The subtle yet crucial differences in platinum-based regimens' safety and synergy with combination treatments need consideration.

Methods

We analyzed cases from the AGAMENON–SEOM Spanish registry of HER2-negative advanced esophagogastric adenocarcinoma treated with platinum and fluoropyrimidine from 2008 to 2021. This study focused exclusively on patients receiving one of the four regimens: FOLFOX (5-FU and oxaliplatin), CAPOX (capecitabine and oxaliplatin), CP (capecitabine and cisplatin) and FP (5-FU and cisplatin). The aim was to determine the most effective and tolerable platinum and fluoropyrimidine-based chemotherapy regimen and to identify any prognostic factors.

Results

Among 1293 patients, 36% received either FOLFOX (n = 468) or CAPOX (n = 466), 20% CP (n = 252), and 8% FP (n = 107). FOLFOX significantly increased PFS (progression free survival) compared to CP, with a hazard ratio of 0.73 (95% CI 0.58–0.92, p = 0.009). The duration of treatment was similar across all groups. Survival outcomes among regimens were similar, but analysis revealed worse ECOG–PS (Eastern Cooperative Oncology Group–Performance Status), > 2 metastatic sites, bone metastases, hypoalbuminemia, higher NLR (neutrophil-to-lymphocyte ratio), and CP regimen as predictors of poor PFS. Fatigue was common in all treatments, with the highest incidence in FOLFOX (77%), followed by FP (72%), CAPOX (68%), and CP (60%). Other notable toxicities included neuropathy (FOLFOX 69%, CAPOX 62%), neutropenia (FOLFOX 52%, FP 55%), hand–foot syndrome in CP (46%), and thromboembolic events (FP 12%, CP 11%).

Conclusions

FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.