OBJECTIVES: Quality of life (QoL) is an important treatment goal alongside increasing survival in metastatic colorectal cancer (mCRC). We estimated the QoL impact of adverse events (AE) associated with fruquintinib, trifluridine/tipiracil (T/T), regorafenib, and T/T+bevacizumab (T/T+bev) for mCRC previously treated with standard therapies and biologics.

METHODS: EuroQoL-5-Dimension-5-Level (EQ-5D-5L) patient-level data (assessing mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) from the phase 3 randomized clinical trial (Ph3 RCT) FRESCO-2 comparing fruquintinib + best supportive care (BSC) vs. placebo+BSC were analyzed using utility value sets from Australia, Belgium, Canada, Denmark, Germany, Italy, Japan, Portugal, Singapore, South Korea, Spain, UK, and USA. Multiple univariate and multivariate mixed-effects, repeated-measures, linear regression models were conducted with random intercept for each patient, fixed predictors (randomized treatment, baseline age, sex, baseline utility, prior treatment) and time-variant health state covariates (progression status, ongoing AEs grade ≥3). Grade ≥3 AE rates were from Ph3 RCTs FRESCO and FRESCO-2 for fruquintinib (61.2% and 63.0%), RECOURSE and SUNLIGHT for T/T (69.0% and 69.5%), SUNLIGHT for T/T+bev (72.4%), and CORRECT for regorafenib (78.0%). If statistically significant in the final multivariate model, the ongoing AEs grade ≥3 coefficient was multiplied by the rate of AEs grade ≥3 of each comparator to estimate their AE-associated utility decrement.

RESULTS: No fixed predictor reached statistical significance, including randomized treatment. Progression and ongoing AEs grade ≥3 were statistically significant (p<0.0001); for illustration, 0.0448 and 0.1041 in Spain, respectively. AEs utility decrement was 0.064 and 0.066 for fruquintinib (FRESCO and FRESCO-2); 0.072 (both RECOURSE and SUNLIGHT); 0.075 for T/T+bev; and 0.081 for regorafenib. Results were similar across countries.

CONCLUSIONS: AE-associated utility decrement was double that of disease progression, highlighting the significant impact of AEs on QoL. Fruquintinib was associated with lower AE-associated QoL decrement versus regorafenib, T/T and T/T+bev for patients with mCRC previously treated with standard therapies and biologics.