Patient-reported outcomes in a phase II randomised study of regorafenib compared with lomustine in patients with relapsed glioblastoma (the REGOMA trial)

Abstract

Background: The REGOMA trial showed that regorafenib significantly improved overall survival in patients with recurrent glioblastoma compared with lomustine. Patients treated with regorafenib experienced a higher occurrence of grade 3-4 drug-related adverse events than those receiving the standard treatment. Because this safety profile was expected, it was considered of great importance to assess the patient point of view regarding the disease and treatment impact on different aspects of life and patient well-being. We here report the final results of the health-related quality of life (HRQoL) assessment, a secondary end-point of the study. This trial is registered with ClinicalTrials.gov, NCT02926222.

Methods: Patient-reported outcomes were assessed, within a prospective, randomised, multicentre, open-label phase II trial, by the European Organisation for Research and Treatment of Cancer core questionnaire and brain module at baseline and every 8-weekly neuroradiological assessment till disease progression. Mixed-effect linear models were fitted for each of the HRQoL domain to examine the change over progression-free time within and between arms. Furthermore, differences were also classified as clinically meaningful changes. To correct for multiple comparisons and avoid type I errors, the level of significance was set at P = 0.01 (2-sided).

Results: Of 119 enrolled patients, 56/59 (95%) patients and 58/60 (97%) patients treated with regorafenib and lomustime completed questionnaires at baseline, respectively. No significant differences were observed in any generic or cancer-specific domain during treatment in both arms, or between the two arms, except for the appetite loss and diarrhoea scales which were significantly worse in patients treated with regorafenib. The rate of patients with a clinically meaningful worsening for appetite loss, diarrhoea and for any other domain was not statistically different between the two arms.

Conclusions: Regorafenib did not negatively affect HRQoL in patients with recurrent glioblastoma. These data combined with the survival benefit shown in the REGOMA trial support the use of regorafenib as a treatment option for these patients.

Keywords: Glioblastoma; Health-related quality of life; Lomustine; Patient-reported outcome; Randomised phase II trial; Regorafenib.