Andrew J Martin, Yu Yang Soon, Katrin Marie Sjoquist, Nick Pavlakis, David Goldstein, Kohei Shitara, John R Simes
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INTEGRATE 2a (I2a, phase 3) demonstrated an overall survival (OS) benefit, alone and in a pre-specified pooled analysis with I1.</p><p><strong>Aim: </strong>To evaluate HRQoL outcomes from I2a and the pooled analysis with I1.</p><p><strong>Methods: </strong>HRQoL was assessed at baseline, day 1 of each cycle, and every 8 weeks until progression, using EORTC QLQ-C30, EORTC STO22, and the participant Disease and Treatment Assessment (PtDATA). The primary endpoint was deterioration-free survival (DetFS), defined as time to a ≥ 10-point decline in QLQ-C30 physical function (DetFSPF) or global health status (DetFSGHS), progression, or death. Secondary analyses used linear mixed models (LMM). Tertiary analyses used logistic regression to evaluate symptom and side-effect prevalence (PtDATA). Pooled analyses adjusted for trial effects.</p><p><strong>Results: </strong>Of 251 I2a participants, 240 contributed HRQoL data. 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引用次数: 0
摘要
背景：INTEGRATE试验评估了瑞非尼在晚期胃癌和食管胃结癌（AGOC）中的治疗效果，这是一种预后不良的人群。在INTEGRATE 1 （I1, 2期）中，瑞戈非尼改善了无进展生存期（PFS），而没有出现健康相关生活质量（HRQoL）的明显过度下降。INTEGRATE 2a （I2a， 3期）在单独和预先指定的I1合并分析中证明了总生存期（OS）的益处。目的：评价I2a及I1合并分析的HRQoL结果。方法：采用EORTC QLQ-C30、EORTC STO22和参与者疾病与治疗评估（PtDATA），在基线、每个周期第1天和每8周评估HRQoL，直至进展。主要终点是无恶化生存期（DetFS），定义为QLQ-C30身体功能（DetFSPF）或整体健康状态（DetFSGHS）、进展或死亡下降≥10个点的时间。二次分析采用线性混合模型（LMM）。第三级分析采用逻辑回归评估症状和副作用发生率（PtDATA）。合并分析调整了试验效应。结果：在251 I2a参与者中，240人提供了HRQoL数据。Regorafenib在DetFSPF （HR = 0.75, 95% CI 0.58-0.99, p = 0.03）和DetFSGHS （HR = 0.68, 95% CI 0.52-0.89, p = 0.004）上均优于Regorafenib。LMM组HRQoL轨迹无明显差异。瑞非尼组皮疹、手足综合征、麻木和应对困难更常见。综合分析证实了这些发现。结论：瑞非尼可适度延长AGOC患者的生存期，无明显HRQoL恶化。尽管毒性更频繁，但总体HRQoL得以保留。当考虑到生存和HRQoL偏好时，Regorafenib可能提供净临床益处。
Health-related quality-of-life outcomes with regorafenib in advanced gastric and esophagogastric junction cancer: results from the INTEGRATE trials.
Background: The INTEGRATE trials evaluated regorafenib in advanced gastric and esophagogastric junction cancer (AGOC), a poor prognosis population. In INTEGRATE 1 (I1, phase 2), regorafenib improved progression-free survival (PFS) without a clear excess decline in health-related quality of life (HRQoL). INTEGRATE 2a (I2a, phase 3) demonstrated an overall survival (OS) benefit, alone and in a pre-specified pooled analysis with I1.
Aim: To evaluate HRQoL outcomes from I2a and the pooled analysis with I1.
Methods: HRQoL was assessed at baseline, day 1 of each cycle, and every 8 weeks until progression, using EORTC QLQ-C30, EORTC STO22, and the participant Disease and Treatment Assessment (PtDATA). The primary endpoint was deterioration-free survival (DetFS), defined as time to a ≥ 10-point decline in QLQ-C30 physical function (DetFSPF) or global health status (DetFSGHS), progression, or death. Secondary analyses used linear mixed models (LMM). Tertiary analyses used logistic regression to evaluate symptom and side-effect prevalence (PtDATA). Pooled analyses adjusted for trial effects.
Results: Of 251 I2a participants, 240 contributed HRQoL data. Regorafenib was superior on DetFSPF (HR = 0.75, 95% CI 0.58-0.99, p = 0.03) and DetFSGHS (HR = 0.68, 95% CI 0.52-0.89, p = 0.004). LMM showed no appreciable differences in HRQoL trajectories. Rash, hand-foot syndrome, numbness, and coping difficulties were more frequent with regorafenib. Pooled analyses confirmed these findings.
Conclusion: Regorafenib modestly prolonged survival in AGOC without clear HRQoL deterioration. Despite more frequent toxicities, overall HRQoL was preserved. Regorafenib may offer a net clinical benefit when survival and HRQoL preferences are considered.
期刊介绍：
Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide.
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