A randomized phase III study of fractionated docetaxel, oxaliplatin, capecitabine (low-tox) vs epirubicin, oxaliplatin and capecitabine (eox) in patients with locally advanced unresectable or metastatic gastric cancer: the lega trial

Gastric Cancer. 2022 Jul;25(4):783-793. doi: 10.1007/s10120-022-01292-y. Epub 2022 Mar 30.

Abstract

Background: EOX (epirubicin, oxaliplatin, and capecitabine) is one of the standard regimens for metastatic or locally advanced gastric cancer (GC). A new combination based on fractional docetaxel (low-TOX) has been developed in an attempt to increase the efficacy of EOX and reduce the heavy toxicity of classical docetaxel regimens.

Methods: Overall, 169 previously untreated GC patients were randomized between EOX (arm A) and low-TOX (arm B). The primary endpoint was progression-free survival (PFS), while secondary ones were overall survival (OS), overall response rate (ORR), disease control rate (DCR), and tolerability. The study was designed to detect a 35% (80% power at a two-sided 5% significance level) PFS increase with low-TOX and an interim analysis for futility was planned after the first 127 events.

Results: At the cut-off date of interim analysis, median PFS was 6.3 months [95% confidence interval (CI) 5.0-8.1] in arm A vs 6.3 months (95% CI 5.0-7.8) in arm B, without statistical difference. OS was comparable in the two arms: 12.4 in arm A (95% CI 9.1-19.2) vs 11.5 months in arm B (95% CI 8.6-15.0). ORR was 33% and 24%, while DCR was 68% and 67%, respectively. Treatment modification (91% vs 78%, P = 0.017) and number of patients with CTC grade ≥ 3 adverse events (42 vs 35) were higher in arm B.

Conclusions: A triplet regimen based on the fractional dose of docetaxel achieves no improvement over EOX which remains a potential standard treatment in many patients with inoperable, locally advanced or metastatic GC.

Keywords: Advanced gastric cancer; EOX; LEGA trial; Low-TOX; Triplet regimen.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Capecitabine / adverse effects
  • Docetaxel
  • Epirubicin
  • Fluorouracil / adverse effects
  • Humans
  • Oxaliplatin
  • Stomach Neoplasms* / pathology
  • Treatment Outcome

Substances

  • Oxaliplatin
  • Docetaxel
  • Epirubicin
  • Capecitabine
  • Fluorouracil