621PBiweekly TAS-102 and bevacizumab as a third-line chemotherapy for metastatic colorectal cancer: A phase II multicenter clinical trial (TAS-CC4 study)

Background TAS-102 improved overall survival of metastatic colorectal cancer (mCRC) patients with median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, the combination of TAS-102 and bevacizumab (BV) has been shown to extend median PFS to 3.7 months (C-TASK FORCE). However, this study included patients with 2nd line and 3rd line chemotherapy. Furthermore, combination chemotherapy of TAS-102 plus BV was reportedly associated with grade ≥3 neutropenia in 72% of treated patients. This study was designed for patients being treated as 3rd line chemotherapy to investigate the clinical impact of this combination and whether neutropenia could be suppressed by altering the TAS-102 administration protocol (biweekly method). Methods This phase II study was conducted in investigator-initiated, open-label, single-arm, multicenter manner in Japan. Eligible patients were 20-80 years old and had to have an ECOG performance status of 0 or 1; had confirmed unresectable mCRC with histologically diagnosed adenocarcinoma; had previously administrated first- and second-line chemotherapy for mCRC and whose tumors were diagnosed as progression of disease (PD). TAS-102 (35 mg/ m²) was given orally twice daily on days 1 -5 and 15 -19 in a 4-weeks cycle, and BV (5 mg/ kg) was administered by intravenous infusion for 30 min in every 2 weeks. The primary endpoint was PFS, and the secondary endpoints were response rate (RR), disease control rate (DCR), overall survival (OS), and safety. This study was registered at the University Hospital Medical Information Network, as UMIN#000030030. Results Between January 1, 2018, and March 31, 2019, 45 patients with mCRC were enrolled in this study (median age, 63; male, 51%). The median PFS was 121 days. The RR and DCR were 4.4% and 73.3%, respectively. Grade 3 or higher adverse events were hypertension (20.0%), neutropenia (15.5 %), leukopenia (6.7 %), fatigue (6.7 %), anemia (4.4 %), anorexia (2.2 %), nausea (2.2 %), creatinine increased (2.2 %) and proteinuria (2.2 %). No treatment-related deaths occurred. Conclusions Biweekly administration of TAS-102 and BV prevents neutropenia and could be one of the treatment options for 3rd line chemotherapy for mCRC. Clinical trial identification UMI30030. 2018/March/01. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.