A new study published in Cancer Management and Resources has found that regorafenib (Stivarga®) delays the deterioration of health-related quality of life (HRQOL) in patients with advanced gastrointestinal stromal tumor (GIST) as well as metastatic colorectal cancer (mCRC) and hepatocellular carcinoma (HCC).

The post-hoc study combined HRQOL data from 4 phase 3 clinical trials: 2 trials for mCRC (CORRECT, NCT01103323; CONCUR, NCT01584830), 1 for GIST (GRID, NCT01271712), and 1 for HCC (RESORCE, NCT01774344).

The pooled analyses showed that the median time until definitive deterioration (TUDD) ranged from 16.3 to 24.1 weeks for patients in the regorafenib group, compared to 8.6 to 12.1 weeks for the placebo group, depending on which HRQOL scale was being used. Log-rank test results from Kaplan-Meier analysis of the data showed that the treatment TUDDs were significantly longer than placebo (P values  ≤.04 for all scales). Additional evidence for delayed TUDD with regorafenib was provided by Cox regression, which showed hazard ratio (HR) values between 0.61 and 0.81 in favor of regorafenib.


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To assess HRQOL, multiple patient-reported outcomes including the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol-5D (EQ5D) were collected. Previous individual clinical trial analyses of these factors showed no difference in time to first deterioration (TDD) between regorafenib and placebo. The authors argued that TUDD was a better measure than TDD, however, since it accounted for initial adverse events due to drug toxicity which necessitated dose modifications early in treatment. As stated in the paper, “the TUDD analysis may be more appropriate and a better measure of HRQOL with regorafenib in the metastatic setting, where dose adjustments are important for optimizing tolerability and allowing patients to continue treatment.”

In the clinical trial for GIST, called GRID, a total of 199 patients were enrolled in the study from hospitals located across Asia, Europe, North America, and the Middle East with 133 receiving regorafenib while 66 received placebo. Of these 199 patients, 185 were included in the pooled analysis of 1699 patients in this study. Previously reported trial data showed that the patients receiving regorafenib had a median progression-free survival of 4.8 months compared to 0.9 months in the placebo group resulting in an HR of 0.27 (95% CI, 0.19-0.39). 

Regorafenib is an oral multikinase inhibitor developed by Bayer that is approved by the US Food and Drug Administration (FDA) for use in the treatment of mCRC, GIST, and HCC. It is believed to work through targeting angiogenic-related receptors and oncogenic kinases to inhibit angiogenesis.

References

Hofheinz R-D, Bruix J, Demetri GD, et al. Effect of regorafenib in delaying definitive deterioration in health-related quality of life in patients with advanced cancer of three different tumor types. Cancer Manag Res. 2021;13:5523-5533. doi:10.2147/CMAR.S305939

Study of regorafenib as a 3rd-line or beyond treatment for gastrointestinal stromal tumors (GIST) (GRID). US National Library of Medicine. ClinicalTrials.gov. Accessed July 26, 2021.

Demetri GD, Reichardt P, Kang Y-K, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):295-302. doi:10.1016/S0140-6736(12)61857-1

STIVARGA® (regorafenib). Bayer. Accessed July 26, 2021.