Scherpereel Arnaud, Antonia Scott, Bautista Yolanda, Grossi Francesco, Kowalski Dariusz, Zalcman Gérard, Nowak Anna K, Fujimoto Nobukazu, Peters Solange, Tsao Anne S, Mansfield Aaron S, Popat Sanjay, Sun Xiaowu, Lawrance Rachael, Zhang Xiaoqing, Daumont Melinda J, Bennett Bryan, McKenna Mike, Baas Paul
Pulmonary and Thoracic Oncology Department, University of Lille, CHU Lille, INSERM, OncoThAI, Institut Coeur Poumon, Boulevard du Professeur Jules Leclercq, 59037 Lille, France.
Thoracic Oncology Department, H. Lee Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.
Lung Cancer. 2022 May;167:8-16. doi: 10.1016/j.lungcan.2022.03.012. Epub 2022 Mar 21.
In CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient-reported outcomes (PROs).
Patients (N = 605) were randomized to nivolumab + ipilimumab or chemotherapy. Changes in disease-related symptom burden and health-related quality of life (HRQoL) were evaluated descriptively using the Lung Cancer Symptom Scale (LCSS)-Mesothelioma (Meso) average symptom burden index (ASBI), LCSS-Meso 3-item global index (3-IGI), 3-level EuroQol 5-dimensional (EQ-5D-3L) visual analog score (VAS), and EQ-5D-3L utility index. PROs were assessed at baseline and every 2 (nivolumab + ipilimumab) or 3 weeks (chemotherapy) through 12 weeks, every 6 weeks through 12 months, every 12 weeks thereafter, and at specified follow-ups. Mixed-effect model repeated measures (MMRM) and time to deterioration analyses were conducted.
Completion rates were generally >80%. LCSS-Meso ASBI mean changes from baseline trended to improve over time with nivolumab + ipilimumab and deteriorate with chemotherapy, but did not meet clinically important difference thresholds [±10 score change]. EQ-5D-3L VAS mean scores improved over time with nivolumab + ipilimumab; by week 60, patients had scores consistent with United Kingdom normal population values. MMRM analyses favored nivolumab + ipilimumab for all individual symptoms except cough. Nivolumab + ipilimumab delayed time to definitive deterioration in HRQoL (hazard ratio 0.52 [95% confidence interval 0.36-0.74]) and showed a trend in symptom delay versus chemotherapy.
Nivolumab + ipilimumab decreased the risk of deterioration in disease-related symptoms and HRQoL versus chemotherapy and maintained QoL in patients with unresectable MPM.
在CheckMate 743（NCT02899299）试验中，纳武利尤单抗联合伊匹木单抗显著延长了不可切除恶性胸膜间皮瘤（MPM）患者的总生存期。我们报告了患者报告结局（PRO）。
患者（N = 605）被随机分为纳武利尤单抗联合伊匹木单抗组或化疗组。使用肺癌症状量表（LCSS）-间皮瘤（Meso）平均症状负担指数（ASBI）、LCSS-Meso 3项综合指数（3-IGI）、3级欧洲五维健康量表（EQ-5D-3L）视觉模拟评分（VAS）和EQ-5D-3L效用指数，对疾病相关症状负担和健康相关生活质量（HRQoL）的变化进行描述性评估。在基线时以及每2周（纳武利尤单抗联合伊匹木单抗组）或3周（化疗组）直至12周、每6周直至12个月、此后每12周以及在特定随访时评估PRO。进行了混合效应模型重复测量（MMRM）和恶化时间分析。
完成率总体>80%。纳武利尤单抗联合伊匹木单抗治疗时，LCSS-Meso ASBI相对于基线的平均变化随时间推移呈改善趋势，化疗时则呈恶化趋势，但未达到具有临床意义的差异阈值[±10分变化]。纳武利尤单抗联合伊匹木单抗治疗时，EQ-5D-3L VAS平均评分随时间推移有所改善；到第60周时，患者的评分与英国正常人群值一致。MMRM分析显示，除咳嗽外，纳武利尤单抗联合伊匹木单抗对所有个体症状均更有利。纳武利尤单抗联合伊匹木单抗延迟了HRQoL明确恶化的时间（风险比0.52[95%置信区间0.36 - 0.74]），并且与化疗相比在症状延迟方面呈趋势性优势。
与化疗相比，纳武利尤单抗联合伊匹木单抗降低了不可切除MPM患者疾病相关症状和HRQoL恶化的风险，并维持了患者的生活质量。
