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



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.


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.


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.


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.

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We thank all patients and co-workers for their participation and cooperation in the TAS-CC3 study. We also thank H. Nikki March, PhD, from Edanz Group ( for editing a draft of this manuscript.


The authors received no financial support for the research, authorship, and/or publication of this article.

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Authors and Affiliations




Conception and design: YY, TY, KS, TO, and KK. Acquisition of data: YY, HK, SY, and HK. Analysis and interpretation of data: YY, TY, and TO. Writing, review, and/or revision of the manuscript: YY, TY, and SH. Administrative, technical, or material support: TY and AM. Study supervision: HY, HI, and KK. Other (recruitment of study subjects and oversight of study participants): YY, TY, HK, CK, KI, SY, HK, AF, HS, KY, and AM.

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Correspondence to Yoichiro Yoshida.

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Conflict of interest

Keiichiro Ishibashi has received research funding from Taiho and Chugai. Hideyuki Ishida has received research funding from Taiho and Chugai. Suguru Hasegawa has received research funding from Taiho and Takeda. The other authors declare that they have no competing interest.

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Yoshida, Y., Yamada, T., Kamiyama, H. et al. Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study. Int J Clin Oncol 26, 111–117 (2021).

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