QTWiST analysis of the RECOURSE trial of trifluridine/tipiracil in metastatic colorectal cancer.

Purpose: A Quality-adjusted Time WIthout Symptoms of disease or Toxicity (QTWiST) analysis was carried out to assess quality-adjusted survival time in the RECOURSE trial of trifluridine/tipiracil versus placebo in pretreated metastatic colorectal cancer (mCRC).

Methods: Duration of overall survival in the RECOURSE trial (n=798 patients) was partitioned into three discrete health states: toxicity (TOX), time without symptoms or toxicity (TWIST) and relapse (REL). TOX was defined as time spent with grade 3 or 4 treatment-related adverse events (AEs) after randomisation and before progression or censoring. AEs were limited to those related to trifluridine/tipiracil and known to affect quality of life (QoL) (ie, nausea, vomiting, diarrhoea, fatigue/asthaenia, anorexia and febrile neutropaenia). The estimated mean duration of each state, weighted by a utility coefficient representing QoL, was combined into a global QTWiST score.

Results: In the RECOURSE trial, overall survival was 7.1 months with trifluridine/tipiracil versus 5.3 months with placebo. Patients receiving trifluridine/tipiracil spent longer in each health state than placebo recipients. Using assumed utility coefficients of 1 for TWIST and 0.5 for TOX and REL, the QTWiST was 5.48 months for the trifluridine/tipiracil group and 3.98 months for the placebo group, a difference of 1.5 (95% CI 1.49 to 1.52) months in favour of trifluridine/tipiracil. A sensitivity analysis using large variations in utility coefficients for TOX and REL produced a range of only approximately 0.5 months from minimum to maximum QTWiST.

Conclusions: Quality-adjusted survival, as measured by QTWiST, shows clinically meaningful improvements in patients treated with trifluridine/tipiracil versus placebo in pretreated mCRC.