Effect of Regorafenib in Delaying Definitive Deterioration in Health-Related Quality of Life in Patients with Advanced Cancer of Three Different Tumor Types

Ralf-Dieter Hofheinz; Jordi Bruix; George D Demetri; Axel Grothey; Marisca Marian; Jennifer Bartsch; Dawn Odom

doi:10.2147/CMAR.S305939

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 Jul 12:13:5523-5533. doi: 10.2147/CMAR.S305939. eCollection 2021.

Authors

Ralf-Dieter Hofheinz¹, Jordi Bruix², George D Demetri³, Axel Grothey⁴, Marisca Marian⁵, Jennifer Bartsch⁶, Dawn Odom⁶

Affiliations

¹ Interdisciplinary Tumor Center, University of Heidelberg, Mannheim, Germany.
² Barcelona Clinic Liver Cancer (BCLC) Group, Hospital Clinic. IDIBAPS, University of Barcelona, CIBERehd, Barcelona, Spain.
³ Ludwig Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁴ Gastrointestinal Cancer Research, West Cancer Center, OneOncology, Germantown, TN, USA.
⁵ Oncology, Pharmaceuticals Division of Bayer AG, Basel, Switzerland.
⁶ Department of Biostatistics, RTI Health Solutions, Research Triangle Park, NC, USA.

Abstract

Purpose: The efficacy and safety of regorafenib have been demonstrated in phase 3 trials for multiple tumor types, including metastatic colorectal cancer (mCRC) (CORRECT [NCT01103323]; CONCUR [NCT01584830]), advanced gastrointestinal stromal tumor (GIST) (GRID [NCT01271712]), and hepatocellular carcinoma (HCC) (RESORCE [NCT01774344]). The objective of this post hoc exploratory analysis was to explore the impact of regorafenib on delaying health-related quality of life (HRQOL) deterioration across these tumor types.

Patients and methods: HRQOL data (assessed with EORTC QLQ-C30 and EQ-5D questionnaires) were pooled for all trials to determine time until definitive deterioration (TUDD), defined as the patient's first minimal clinically important deterioration in HRQOL score from baseline that does not resolve, using stratified Kaplan-Meier estimators and Cox proportional hazards models adjusted for relevant trial, cancer type, and baseline covariates. Additional analyses based on cancer type were conducted by pooling mCRC trials (CORRECT and CONCUR) and pooling the two mCRC trials with the HCC trial (RESORCE).

Results: A total of 1699 patients with HRQOL data were pooled across the four trials. The results showed that regorafenib significantly delayed TUDD compared with placebo across all three tumor types. Median time to deterioration across the five scales ranged from 16.3 to 24.1 weeks for regorafenib and 8.6 to 12.1 weeks for placebo. The results from the individual studies, the pooled mCRC trials, and the pooled mCRC and HCC trials were similar to the overall pooled results.

Conclusion: A pooled analysis of four phase 3 trials demonstrated that regorafenib delayed a clinically relevant exploratory endpoint, defined as TUDD, compared with placebo across three different tumor types (mCRC, GIST, and HCC), which supports a novel benefit of the impact of regorafenib with respect to patients with these three types of cancers by allowing initial declines in HRQOL to resolve and patients the opportunity to continue treatment.

Keywords: gastrointestinal cancer; hepatocellular cancer; metastatic colorectal cancer; quality of life; regorafenib.

Grants and funding

The financial support for the study was provided by Bayer AG. The CORRECT, CONCUR, GRID, and RESORCE trials were sponsored by Bayer. RTI Health Solutions received funding under a research contract with Bayer AG to conduct this study and provide editorial support in the form of manuscript writing, styling, and submission.