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

Clin Transl Oncol. 2024 Jul;26(7):1674-1686. doi: 10.1007/s12094-024-03388-6. Epub 2024 Feb 15.

Abstract

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.

Keywords: Advanced esophagogastric cancer; Chemotherapy; Cisplatin; Fluoropyrimidine; Oxaliplatin; Survival.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Capecitabine* / administration & dosage
  • Capecitabine* / therapeutic use
  • Cisplatin* / administration & dosage
  • Cisplatin* / therapeutic use
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / pathology
  • Esophagogastric Junction / pathology
  • Female
  • Fluorouracil* / administration & dosage
  • Fluorouracil* / therapeutic use
  • Humans
  • Leucovorin* / administration & dosage
  • Leucovorin* / adverse effects
  • Leucovorin* / therapeutic use
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin* / administration & dosage
  • Oxaliplatin* / therapeutic use
  • Progression-Free Survival
  • Receptor, ErbB-2* / metabolism
  • Registries*
  • Spain
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / pathology

Substances

  • Fluorouracil
  • Capecitabine
  • Receptor, ErbB-2
  • Leucovorin
  • Oxaliplatin
  • Cisplatin
  • ERBB2 protein, human
  • Organoplatinum Compounds

Supplementary concepts

  • Folfox protocol