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

Abstract

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.

Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician’s Choice

“…This hypothesis is further supported by other phase 3 trials that assessed time to deterioration and also showed longer TTdD in treatment arms with significantly or numerically favourable efficacy. These results were consistent across indications including renal cell carcinoma (in a trial of LEN in combination with PEMBRO or everolimus compared with sunitinib) [ 7 , 19 ], hepatocellular carcinoma (in a non-inferiority trial comparing LEN vs sorafenib) [ 20 , 21 ], and a pooled analysis of four trials comparing regorafenib versus placebo across three tumour types [ 22 ].…”

Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature

“…Regorafenib is a third-line treatment for GIST patients but is also registered as a treatment for hepatocellular carcinoma (HCC) and metastatic colorectal cancer (mCRC). Hofheinz et al pooled HRQoL data of patients treated with regorafenib in four trials, including GIST, HCC, and mCRC patients [ 154 ]. Across all tumor types, regorafenib significantly delayed the patient’s first clinical important deterioration in HRQoL score, with the median time to HRQoL deterioration ranging from 16–24 weeks for regorafenib compared to 8–12 weeks for placebo.…”

Regorafenib versus Cabozantinib as a Second-Line Treatment for Advanced Hepatocellular Carcinoma: An Anchored Matching-Adjusted Indirect Comparison of Efficacy and Safety

“…And for patients who progress from sorafenib, regorafenib may offer longer survival and better tolerability and safety than cabozantinib. Furthermore, a recent analysis showed patients' quality of life is significantly better maintained with regorafenib than with placebo [ 31 ]. Further investigations are needed to determine the optimal treatment option for patients progressing from immunotherapy or lenvatinib frontline treatment.…”