Phase II study evaluating trifluridine/tipiracil + bevacizumab and capecitabine + bevacizumab in first-line unresectable metastatic colorectal cancer (mCRC) patients who are non-eligible for intensive therapy (TASCO1): Results of the primary analysis

Introduction: Trifluridine/tipiracil, also known as TAS-102, is a novel chemotherapy approved in patients with mCRC refractory to, or not candidates for standard therapies. A phase I/II study evaluated the combination of trifluridine/tipiracil and bevacizumab in mCRC patients who were refractory to standard therapies and showed encouraging antitumor activity with manageable toxicity (C-TASK FORCE) (Kuboki Y et al. Lancet Oncology, 2017). These promising results led to the initiation of a global non-comparative phase 2 study, TASCO1, to evaluate the efficacy and safety of trifluridine/tipiracil + bevacizumab (TT-B) and capecitabine + bevacizumab (C-B) in first-line unresectable mCRC patients who are non-eligible for standard first-line therapy. Methods: First-line mCRC-patients not candidate for intensive oxaliplatin- or irinotecan-based chemotherapy and without chance for curative resection according to the investigator’s judgment were randomized (in a 1:1 ratio; stratified by RAS status, ECOG performance status and country) to receive trifluridine/tipiracil (35 mg/m2 given orally bid on days 1–5 and 8–12 in a 28-day cycle) plus bevacizumab (5 mg/kg on days 1 and 15 of a 28-day treatment cycle) or capecitabine (1250 or 1000 mg/m²/dose bid on days 1-14 in a 21-day) plus bevacizumab (7.5 mg/kg on day 1 in a 21-day treatment cycle). The primary endpoint was progression-free survival, the secondary endpoints included overall survival, safety and quality of life assessed by EORTC QLQ-C30 and QLQ-CR29 questionnaires. Results: Between Apr 29, 2016 and Mar 29, 2017, 154 patients were randomized and 153 pts were treated with TT-B (n=77) or C-B (n=76). The median PFS was 9.2 months in the TT-B group, 7.8 months in the C-B group. When considering only severe (Grade ≥3) events, a ≥5% difference in incidence between arms was reported for seven Preferred Terms of neutropenia (46.8% with TT-B vs. 5.2% with C-B), neutrophil count decrease (18.2% vs. 1.3%), white blood cell count decrease (10.4% vs. 1.3%), anemia (10.4% vs. 0%), hypertension (13% vs 5.3%), palmar-plantar erythrodysaesthesia syndrome (0% with TT-B vs. 11.8% with C-B) and diarrhea (1.3% vs. 7.9%). Serious events of febrile neutropenia were reported for 3.9% of patients in the TT-B arm, identical to the rate observed in the C-B arm. Further analyses on Quality of Life and biomarkers are on-going and will be presented later. Conclusion: The promising activity of TT-B observed in the C-TASK Force trial was confirmed in the TASCO1 phase 2 trial in 1st line mCRC patients non-eligible for intensive therapy. The opportunity to conduct a global confirmatory phase 3 trial versus C-B is currently being evaluated.