Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study

Int J Clin Oncol. 2021 Jan;26(1):111-117. doi: 10.1007/s10147-020-01794-8. Epub 2020 Oct 21.


Background: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets.

Methods: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety.

Results: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred.

Conclusions: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.

Keywords: Bevacizumab; Chemotherapy; Colorectal cancer; Neutropenia; TAS-102.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / adverse effects
  • Colorectal Neoplasms* / drug therapy
  • Disease-Free Survival
  • Drug Combinations
  • Fluorouracil / therapeutic use
  • Humans
  • Japan
  • Leucovorin / therapeutic use
  • Pyrrolidines
  • Thymine
  • Trifluridine


  • Drug Combinations
  • Pyrrolidines
  • trifluridine tipiracil drug combination
  • Bevacizumab
  • Leucovorin
  • Thymine
  • Trifluridine
  • Fluorouracil