TAS-102, Irinotecan, and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO), a phase II clinical trial

Br J Cancer. 2024 Nov;131(8):1290-1297. doi: 10.1038/s41416-024-02845-x. Epub 2024 Sep 7.

Abstract

Background: The efficacy of FOLFIRI plus an antiangiogenesis biologic agent as 2nd line therapy for metastatic colorectal adenocarcinoma is limited. TAS-102 is a novel oral antimetabolite with a distinct mechanism of action from fluoropyrimidines. We evaluated the antitumour efficacy of TAS-102, irinotecan and bevacizumab in patients with pre-treated, advanced colorectal adenocarcinoma in a multicenter, phase II, single-arm study.

Methods: Patients with advanced colorectal adenocarcinoma who had progressed after oxaliplatin and fluoropyrimidine and were eligible for treatment with bevacizumab were treated with irinotecan, bevacizumab, and TAS-102 in 28-day cycles. The primary endpoint was progression-free survival (PFS).

Results: We enrolled 35 evaluable patients. The study was positive. The median PFS was 7.9 (90% CI 6.2-11.8) months (vs. 6 months in historical control, p = 0.018). The median overall survival was 16.5 (90% CI 9.8-17.5) months. Sixty-seven per cent of patients experienced grade 3 or higher treatment-related adverse events. The most common toxicities were hematological (neutropenia) and gastrointestinal (diarrhoea, nausea, and vomiting).

Conclusions: Irinotecan, TAS-102 and bevacizumab is an active 2nd line therapy for patients with metastatic colorectal adenocarcinoma. Neutropenia is common and can affect dose density/intensity mandating use of G-CSF. A randomized study versus standard-of-care therapy is warranted.

Clinical trial registration: ClinicalTrials.gov NCT04109924.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / adverse effects
  • Bevacizumab* / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Drug Combinations*
  • Female
  • Humans
  • Irinotecan* / administration & dosage
  • Irinotecan* / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Progression-Free Survival
  • Pyrrolidines* / administration & dosage
  • Pyrrolidines* / adverse effects
  • Pyrrolidines* / therapeutic use
  • Thymine*
  • Trifluridine* / administration & dosage
  • Trifluridine* / adverse effects
  • Trifluridine* / therapeutic use
  • Uracil* / administration & dosage
  • Uracil* / analogs & derivatives
  • Uracil* / therapeutic use

Substances

  • Bevacizumab
  • trifluridine tipiracil drug combination
  • Irinotecan
  • Trifluridine
  • Thymine
  • Drug Combinations
  • Uracil
  • Pyrrolidines

Associated data

  • ClinicalTrials.gov/NCT04109924