Department of Medicine and University Cancer Center Leipzig, University of Leipzig Medical Center, Leipzig, Germany.
Digestive Oncology, University Hospitals Gasthuisberg, Leuven, and KULeuven, Leuven, Belgium.
ESMO Open. 2024 Aug;9(8):103663. doi: 10.1016/j.esmoop.2024.103663. Epub 2024 Aug 14.
First-line zolbetuximab plus chemotherapy (SPOTLIGHT, mFOLFOX6; GLOW, CAPOX) significantly improved progression-free survival (PFS) and overall survival (OS) versus placebo plus chemotherapy in patients with human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors were claudin 18 isoform 2-positive in the phase III SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies. We present patient-reported outcomes (PROs) from these studies.
Health-related quality of life (HRQoL) was measured in the full analysis sets using the European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients Core Questionnaire (QLQ-C30) and Oesophago-Gastric Module (QLQ-OG25), Global Pain, and 5-level EQ-5D (EQ-5D-5L) questionnaires. Analyses focused on key PRO domains: global health status (GHS)/QoL, physical functioning, abdominal pain and discomfort, and nausea/vomiting. Least squares mean (LSM) changes from baseline and time to first definitive deterioration (TTDD) were evaluated combined across SPOTLIGHT and GLOW and for individual studies. Time to confirmed deterioration (TTCD) was evaluated independently for SPOTLIGHT and GLOW.
The combined analysis set included 1072 patients (zolbetuximab plus chemotherapy, 537; placebo plus chemotherapy, 535). Compliance rates were similar between treatment arms. Similar trends were observed in the zolbetuximab versus placebo arms for LSM changes from baseline in key PRO domains, with no clinically meaningful deterioration. Nausea/vomiting worsened during the first few zolbetuximab cycles but later returned to baseline levels. Overall TTCD and TTDD results were similar between arms in both studies.
Patients in SPOTLIGHT and GLOW maintained measured HRQoL relative to baseline when treated with first-line zolbetuximab added to chemotherapy. Zolbetuximab plus chemotherapy improved PFS and OS without negatively affecting HRQoL in key PRO domains compared with placebo plus chemotherapy.
在 III 期 SPOTLIGHT（NCT03504397）和 GLOW（NCT03653507）研究中，对于 claudin 18 同种型 2 阳性的人表皮生长因子受体 2 阴性、局部晚期不可切除或转移性胃或胃食管交界处腺癌患者，zolbetuximab 联合化疗（SPOTLIGHT，mFOLFOX6；GLOW，CAPOX）较安慰剂联合化疗显著改善了无进展生存期（PFS）和总生存期（OS）。本研究报告了这些研究的患者报告结局（PRO）。
使用欧洲癌症研究和治疗组织癌症患者生活质量核心问卷（QLQ-C30）和胃食管模块（QLQ-OG25）、全球疼痛和 5 级 EQ-5D（EQ-5D-5L）问卷，在全分析集中测量健康相关生活质量（HRQoL）。分析主要集中在关键 PRO 领域：总体健康状况（GHS）/生活质量、身体功能、腹痛和不适以及恶心/呕吐。从基线到首次明确恶化（TTDD）的最小二乘均数（LSM）变化在 SPOTLIGHT 和 GLOW 以及个体研究中进行了联合评估。SPOTLIGHT 和 GLOW 分别独立评估了确认恶化的时间（TTCD）。
联合分析集包括 1072 例患者（zolbetuximab 联合化疗 537 例，安慰剂联合化疗 535 例）。治疗组的依从率相似。在 zolbetuximab 与安慰剂组中，关键 PRO 领域的 LSM 从基线的变化趋势相似，没有临床意义上的恶化。恶心/呕吐在接受几个 zolbetuximab 周期治疗后恶化，但后来恢复到基线水平。在两项研究中，总体 TTCD 和 TTDD 结果在两组间相似。
在接受一线 zolbetuximab 联合化疗治疗时，SPOTLIGHT 和 GLOW 中的患者与基线相比保持了测量的 HRQoL。与安慰剂联合化疗相比，zolbetuximab 联合化疗改善了 PFS 和 OS，而没有对关键 PRO 领域的 HRQoL 产生负面影响。
