Quality-adjusted time without symptoms or toxicity (Q-TWiST) of patients with metastatic colorectal cancer (mCRC) treated with fruquintinib in a phase II clinical trial.

Abstract

765 Background: In a randomized phase II trial of mCRC patients who have failed at least 2 lines of standard therapy, fruquintinib has demonstrated superior progression free survival (PFS) and overall survival (OS) benefits over placebo. We further assessed the between-treatment difference of quality of life (QoL) using a Q-TWiST analysis, to elucidate the trade-off between adverse events and treatment benefits. Methods: Mean PFS and OS were estimated using the Kaplan-Meier method. OS in Q-TWiST analysis was partitioned into 3 health states: TOX (time with toxicity before progression), TWiST (time without symptoms or toxicity) and REL (time from progression until death). The algorism of Q-TWiST is the sum of the mean durations for the 3 health states, with each state weighted by its respective utility coefficient. The 95% confidence intervals of mean are calculated with z method and the standard error is generated by bootstrap method. The relative Q-TWiST gains of > = 10% and > = 15% are considered as a clinically important and clearly clinically important, respectively (Revicki, 2006). Results: A total of 71 patients were included in this post-hoc analysis. The 47 patients of fruquintinib arm had significant longer PFS, compared with the 24 patients in the placebo arm (mean: 5.0 vs. 2.2 months, difference [95% CI]: 2.8 [1.4, 4.3]). The benefit of OS was numerically superior (mean: 8.6 vs. 6.9 months, difference [95% CI]: 1.7 [-0.5, 4.0]). Patients treated with fruquintinib showed numerically longer overall Q-TWiST (mean: 5.8 vs. 4.4 months, difference [95% CI]: 1.4 [-0.1, 2.9] than those received placebo with the relative gain of 20.3% over OS, assuming the utility during TOX/REL period is 0.5 and that during the TWiST is 1.0. Sensitivity analysis demonstrated that the Q-TWiST gain may range from -0.7% to 41.2% at various utility assignments. Conclusions: In this phase II trial, mCRC patients treated with fruquintinib had clearly clinically important QoL benefit. Further studies with larger sample size are needed to confirm this finding. Clinical trial information: NCT02196688.