First-line trifluridine/tipiracil plus bevacizumab for unresectable metastatic colorectal cancer: SOLSTICE study design.

Trifluridine/tipiracil (TT) is an orally administered combination of the thymidine-based nucleoside analogue trifluridine and the thymidine phosphorylase inhibitor tipiracil hydrochloride, which increases the bioavailability of cytotoxic trifluridine. Encouraging antitumor activity of first-line TT + bevacizumab (TT-B) has been observed in a Phase II study in patients with unresectable metastatic colorectal cancer ineligible for combination oxaliplatin- or irinotecan-based therapy. Here, we describe the design of SOLSTICE (NCT03869892), an open-label, Phase III trial in unresectable metastatic colorectal cancer patients who are not candidates for, or do not require, intensive therapy. The 854 patients were randomized 1:1 to receive first-line TT-B versus capecitabine + bevacizumab. The primary objective is to demonstrate superior progression-free survival with TT-B over capecitabine + bevacizumab. The first patient was enrolled in March 2019.

Proxies of quality of life in metastatic colorectal cancer: analyses in the RECOURSE trial.

BACKGROUND: In 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 METHODS: Enrolled 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. RESULTS: AEs 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. CONCLUSIONS: Analysis 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.