Optimizing Treatment Sequence for Late-line Metastatic Colorectal Cancer Patients Using Trifluridine/Tipiracil and Regorafenib

Clin Colorectal Cancer. 2018 Dec;17(4):274-279. doi: 10.1016/j.clcc.2018.05.012. Epub 2018 Jun 8.

Abstract

Background: Treatment sequencing for patients with refractory metastatic colorectal cancer (mCRC) has been highly debated. The thymidine-based nucleoside trifluridine/tipiracil (TAS-102) and the multikinase inhibitor regorafenib have demonstrated clinical benefits in randomized phase III trials compared with placebo. However, limited data are available on the most optimal therapy sequence involving TAS-102 and regorafenib.

Patients and methods: In the present retrospective, observational, real-life study, clinical data on mCRC patients treated with TAS-102 or an alternative salvage treatment at the Medical University of Vienna and University Hospital Zurich were collected from January 2013 to December 2016.

Results: A total of 85 patients whose disease had progressed during fluoropyrimidine-based therapy (FBT) with or without an antibody were included. The disease control rate in patients treated with TAS-102 after FBT-based treatment was 24% compared with 35% in patients treated with regorafenib after FBT-based treatment (adjusted odds ratio, 1.75; 95% confidence interval, 0.41-7.47; P = .449). The progression-free survival (PFS) and overall survival (OS) for patients treated with TAS-102 was 2.8 months (quartile, 2.0-4.8 months) and 15.9 months, respectively. When the data were analyzed according to the subgroups of patients with or without an FBT-free period, the TAS-102-treated patients with a previous FBT-free interval had a PFS of 3.1 months and OS of 17.7 months compared with a PFS of 2.2 months and OS of 8.1 months for patients who received TAS-102 immediately after FBT.

Conclusion: Our results have confirmed the efficacy of TAS-102 and regorafenib in the real-life setting. The treatment sequence analysis showed a tendency for longer PFS and OS for TAS-102-treated patients after an FBT-free interval. Prospective randomized data are needed to gain more information about the most beneficial therapy sequence in the salvage treatment of mCRC.

Keywords: Metastatic colorectal cancer; Real life study; Regorafenib; TAS-102; Treatment sequence.

Publication types

  • Observational Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Phenylurea Compounds / administration & dosage
  • Prognosis
  • Pyridines / administration & dosage
  • Pyrrolidines
  • Retrospective Studies
  • Survival Rate
  • Thymine
  • Trifluridine / administration & dosage
  • Uracil / analogs & derivatives

Substances

  • Drug Combinations
  • Phenylurea Compounds
  • Pyridines
  • Pyrrolidines
  • trifluridine tipiracil drug combination
  • regorafenib
  • Uracil
  • Thymine
  • Trifluridine