TAS-102 improved overall survival of refractory colorectal cancer patients with median progression free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, the combination of TAS-102 and Bevacizumab has been shown to extend median PFS with 3.7 months (C-TASK FORCE). However, this study included patients with 2nd line and 3rd line chemotherapy. Our study was planned exclusively for patients receiving this combination as the 3rd line chemotherapy to investigate clinical impact of this combination beyond cytotoxic doublet.
This phase II study was conducted in investigator-initiated, open-label, single-arm, multicentered manner in Japan. Eligible patients were 20-80 years old, and had to have an Eastern Cooperative Oncology Group performance status of 0 or 1; had confirmed unresectable metastatic colorectal cancer (mCRC) with histologically diagnosed adenocarcinoma; were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in the 1st and the 2nd line chemotherapy; and had no previous treatment with regorafenib. TAS-102 (35 mg/ m²) was given orally twice daily on days 1–5 and 8–12 in a 4-weeks cycle, and bevacizumab (5 mg/ kg) was administered by intravenous infusion for 30 minutes in every 2 weeks. The primary endpoint was progression free survival (PFS), and the secondary endpoints were time to treatment failure (TTF), response rate (RR), overall survival (OS), and safety.
Between June 1, 2016, and August 31, 2017, 32 patients with mCRC were enrolled in this study. The median PFS was 4.5 months. Partial response was observed in 2 patients. The most common adverse events above grade 3 were neutropenia (15 patients) followed by thrombocytopenia (4 patients). Treatment-related serious adverse events were reported in one patient. There were no non-hematologic adverse events above grade 3. No treatment-related deaths occurred.
This is the first study which involves the combination of TAS-102 and Bevacizumab as the 3rd line chemotherapy in the setting beyond cytotoxic doublet, and showed to improve PFS for the patients with mCRC. This combination has a potential to be one of therapeutic options of the 3rd line chemotherapy for mCRC.
Clinical trial identification
University Hospital Medical Information Network UMIN#000022438.
Legal entity responsible for the study
TAS-CC3 Study Group.
Has not received any funding.
All authors have declared no conflicts of interest.