BACKGROUND: Regorafenib is approved for patients with metastatic and/or advanced gastrointestinal (GIST), colorectal (CRC), and hepatocellular (HCC) cancers. Individual phase 3 trials have shown that health-related quality of life (HRQOL) is maintained while progression-free survival and overall survival are extended. Exploratory analyses were conducted to assess the effect of regorafenib on HRQOL pooled across all three tumor types. Pooling the trials allows for a more in-depth analysis due to the larger sample size and increased power.
METHODS: HRQOL data were pooled across four regorafenib trials: CORRECT (mCRC), CONCUR (mCRC), GRID (GIST), and RESORCE (HCC). Study design and baseline and demographics characteristics were reviewed to assess the appropriateness of pooling studies. EQ-5D was collected in all four trials, and EORTC QLQ-C30 was collected in all trials except RESORCE. Due to their appropriateness in the metastatic setting, time-until-definitive-deterioration (TUDD) analyses were conducted where an event was defined as the first occurrence of a minimal clinically important reduction from baseline in HRQOL that does not resolve. Established minimal clinically important differences were used: 7 and 0.08 points for the EQ-5D VAS and Index, respectively, and 10 points for the EORTC QLQ-C30, where the summary score, global health status/quality of life, and physical functioning scales were selected a priori for analysis. TUDD was analyzed using stratified Kaplan-Meier estimators and Cox proportional hazard models adjusted for trial and baseline covariates.
RESULTS: A total of 1,699 patients with HRQOL data were pooled across the four trials with 1,516 contributing to the TUDD analyses. Kaplan-Meier results showed TUDD was significantly longer with regorafenib than placebo for all scales (log-rank P values ≤ 0.04). Hazard ratios ranged from 0.61 to 0.81 in favor of regorafenib. Cancer type was a significant covariate in the model, with GIST and HCC demonstrating longer TUDD than CRC. A sensitivity analysis was also performed to compare the results from the pooled analysis with the individual studies. The results from the individual studies were similar to the pooled results but not consistently significant.
CONCLUSIONS: A pooled analysis of four clinical trials shows that regorafenib delays TUDD compared with placebo across tumor types, demonstrating the long-term impact of regorafenib with respect to patients’ HRQOL.
