在复发胶质母细胞瘤患者中比较regorafenib 与洛莫司汀的 II 期随机研究中的患者报告结局（REGOMA 试验）。

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

机构信息

Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.

Clinical Research Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.

出版信息

Eur J Cancer. 2021 Sep;155:179-190. doi: 10.1016/j.ejca.2021.06.055. Epub 2021 Aug 10.

DOI:10.1016/j.ejca.2021.06.055

PMID:34388515

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.

摘要

背景

REGOMA 试验表明，与洛莫司汀相比，regorafenib 可显著改善复发性胶质母细胞瘤患者的总生存期。接受regorafenib 治疗的患者发生 3-4 级药物相关不良事件的发生率高于接受标准治疗的患者。由于这种安全性特征是预期的，因此评估患者对疾病的看法以及治疗对生活和患者福祉不同方面的影响非常重要。我们在此报告该研究的次要终点——健康相关生活质量（HRQoL）评估的最终结果。该试验在 ClinicalTrials.gov 注册，编号为 NCT02926222。

方法

在一项前瞻性、随机、多中心、开放标签的 II 期试验中，通过欧洲癌症研究与治疗组织核心问卷和脑模块，在基线和每 8 周进行神经影像学评估直至疾病进展时，评估患者报告的结果。对于每个 HRQoL 域，都使用混合效应线性模型来检查无进展生存期内和两个治疗臂之间的变化。此外，还将差异分类为具有临床意义的变化。为了校正多重比较和避免 I 类错误，将显著性水平设置为 P=0.01（双侧）。

结果

在纳入的 119 名患者中，分别有 56/59（95%）名接受 regorafenib 和 lomustime 治疗的患者和 58/60（97%）名患者在基线时完成了问卷。在两个治疗臂中，或在两个治疗臂之间，除了接受 regorafenib 治疗的患者的食欲丧失和腹泻评分明显更差之外，在任何通用或癌症特异性域中，在治疗期间均未观察到显著差异。在两个治疗臂之间，食欲丧失、腹泻和任何其他域的患者具有临床意义恶化的发生率没有统计学差异。