Background:We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TTeB) and capecitabine plus bevacizumab (CeB) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. Patients and methods: From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TTeB (N ¼ 77) or CeB (N ¼ 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety. Results: Median (range) duration of treatment was 7.8 (6.0e9.7) months and 6.2 (4.1e9.1) months in the TTeB and CeB groups, respectively. Median (range) PFS was 9.2 (7.6e11.6) and 7.8 (5.5e10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TTeB had more grade !3 neutropenia (47% versus 5% with CeB). Patients receiving CeB had more grade !3 handefoot syndrome (12% versus 0% with TTeB) and grade !3 diarrhea (8% versus 1% with TTeB), consistent with the known safety profiles of these agents. Conclusion: TTeB treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL. Clinical trial information: NCT02743221 (ClinicalTrials.gov)

BackgroundIn the pivotal phase III, randomised, double-blind, placebo-controlled RECOURSE study, treatment with trifluridine/tipiracil was well tolerated and associated with prolonged progression-free and overall survival in patients with metastatic colorectal cancer (mCRC). There was no formal analysis of quality of life (QoL) in RECOURSE. The aim of the present analysis was to assess proxies of QoL during the RECOURSE treatment period, in terms of adverse events (AEs) likely to affect QoL and Eastern Cooperative Oncology Group performance status (ECOG PS).Patients and methodsEnrolled patients had documented, previously treated (≥2 prior chemotherapy lines) mCRC and an ECOG PS of 0 or 1. Patients received best supportive care plus trifluridine/tipiracil 35 mg/m2 twice daily (n=534) or placebo (n=266) in a 28-day cycle. AEs analysed included nausea, vomiting, diarrhoea, dysgeusia and fatigue/asthenia. ECOG PS was determined at baseline, on day 1 of each treatment cycle, at treatment end and 30 days post-treatment discontinuation.ResultsAEs that affect QoL were more frequent in patients treated with trifluridine/tipiracil than placebo. Median treatment duration for patients experiencing at least one of these AEs was longer than that observed for the overall RECOURSE population (trifluridine/tipiracil: 12 vs 7 weeks; placebo: 10 vs 6 weeks). Versus placebo, the duration of most AEs was longer in trifluridine/tipiracil recipients; however, all AEs except nausea and vomiting occupied a lower proportion of the total treatment period. Of the patients who had their PS recorded at discontinuation, PS was maintained in 67% and 63% of trifluridine/tipiracil and placebo recipients, and 84% and 81% of the trifluridine/tipiracil and placebo patients remained at a PS of 0 or 1 at discontinuation.ConclusionsAnalysis of ECOG PS and AEs thought to affect QoL in the RECOURSE patient population suggests that trifluridine/tipiracil treatment does not result in a deterioration of patient QoL versus placebo.

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