Abstract：
BACKGROUND: Tebentafusp demonstrated a superior overall survival (OS) benefit [hazard ratio (HR) 0.51] compared to investigator\'s choice (82% pembrolizumab) in a randomized, phase III trial (IMCgp100-202; N = 378) in untreated metastatic uveal melanoma (mUM). The 1-year OS rates for tebentafusp and pembrolizumab were 73% and 59%, respectively. In the single-arm GEM1402 (N = 52), the 1-year OS rate for nivolumab plus ipilimumab (N+I) in mUM was 52%. Due to limitations in conducting randomized trials in mUM, we compared OS on tebentafusp or pembrolizumab (IMCgp100-202) to N+I (GEM1402) in untreated mUM using propensity scoring methods.
METHODS: Analyses were adjusted using propensity score-based inverse probability of treatment weighting (IPTW), balancing age, sex, baseline lactate dehydrogenase (LDH), baseline alkaline phosphatase, disease location, Eastern Cooperative Oncology Group status, and time from primary diagnosis to metastasis. OS was assessed using IPT-weighted Kaplan-Meier and Cox proportional hazard models. Sensitivity analyses using alternative missing data and weights methods were conducted.
RESULTS: The primary IPTW analysis included 240 of 252 patients randomized to tebentafusp from IMCgp100-202 and 45 of 52 N+I-treated patients from GEM-1402. Key baseline covariates, including LDH, were generally well balanced before weighting. The IPTW-adjusted OS favored tebentafusp, HR 0.52 [95% confidence interval (CI) 0.35-0.78]; 1-year OS was 73% for tebentafusp versus 50% for N+I. Sensitivity analyses showed consistent superior OS for tebentafusp with all IPTW HRs ≤0.61. IPTW analysis of pembrolizumab versus N+I showed no significant difference in OS (HR 0.72; 95% CI 0.50-1.06).
CONCLUSIONS: Tebentafusp was previously shown to provide an OS benefit compared to checkpoint inhibitors or chemotherapy in untreated mUM. Propensity score analysis demonstrated a similar OS benefit for tebentafusp compared with N+I. These data further support tebentafusp as the standard of care in previously untreated human leukocyte antigen (HLA)-A∗02:01+ adult patients with mUM.
METHODS: Analyses were adjusted using propensity score-based inverse probability of treatment weighting (IPTW), balancing age, sex, baseline lactate dehydrogenase (LDH), baseline alkaline phosphatase, disease location, Eastern Cooperative Oncology Group status, and time from primary diagnosis to metastasis. OS was assessed using IPT-weighted Kaplan-Meier and Cox proportional hazard models. Sensitivity analyses using alternative missing data and weights methods were conducted.
RESULTS: The primary IPTW analysis included 240 of 252 patients randomized to tebentafusp from IMCgp100-202 and 45 of 52 N+I-treated patients from GEM-1402. Key baseline covariates, including LDH, were generally well balanced before weighting. The IPTW-adjusted OS favored tebentafusp, HR 0.52 [95% confidence interval (CI) 0.35-0.78]; 1-year OS was 73% for tebentafusp versus 50% for N+I. Sensitivity analyses showed consistent superior OS for tebentafusp with all IPTW HRs ≤0.61. IPTW analysis of pembrolizumab versus N+I showed no significant difference in OS (HR 0.72; 95% CI 0.50-1.06).
CONCLUSIONS: Tebentafusp was previously shown to provide an OS benefit compared to checkpoint inhibitors or chemotherapy in untreated mUM. Propensity score analysis demonstrated a similar OS benefit for tebentafusp compared with N+I. These data further support tebentafusp as the standard of care in previously untreated human leukocyte antigen (HLA)-A∗02:01+ adult patients with mUM.
摘要：
背景：Tebentafusp在一项随机研究中，与研究者的选择（82%pembrolizumab）相比，显示出较好的总生存期（OS）获益（风险比[HR]0.51），未经治疗的转移性葡萄膜黑色素瘤（mUM）的3期试验（IMCgp100-202；N=378）。tebentafusp和pembrolizumab的1年OS率分别为73%和59%，分别。在单臂GEM1402（N=52），nivolumab+ipilimumab(N+I)在mUM中的1年OS率为52%.由于在mUM中进行随机试验的局限性，我们使用倾向评分方法比较了tebentafusp或pembrolizumab(IMCgp100-202)与nivolumab联合ipilimumab(GE1402)在未经治疗的mUM中的OS.
方法：使用基于倾向评分的治疗加权逆概率（IPTW）调整分析，平衡年龄，性别,基线乳酸脱氢酶（LDH），基线碱性磷酸酶，疾病位置,ECOG状态,以及从初次诊断到转移的时间。使用IPT加权Kaplan-Meier和Cox比例风险模型评估OS。使用替代缺失数据和权重方法进行敏感性分析。
结果：主要IPTW分析包括来自IMCgp100-202的随机接受tebentafusp的252名患者中的240名和来自GEM-1402的52名纳武单抗联合ipilimumab治疗的患者中的45名。关键基线协变量，包括LDH在加权之前通常平衡良好。IPTW调整后的操作系统支持tebentafusp，HR0.52（95%置信区间[CI]：0.35，0.78）；tebentafusp的1年OS为73%，N+I为50%。敏感性分析显示，所有IPTWHR≤0.61的tebentafusp具有一致的优异OS。pembrolizumab与N+I的IPTW分析显示OS无显著差异(HR0.72;95%CI:0.50,1.06)。
结论：Tebentafusp先前被证明在未经治疗的mUM中与检查点抑制剂或化疗相比具有OS益处。倾向评分分析表明，与NI相比，tebentafusp的OS益处相似。这些数据进一步支持tebentafusp作为先前未治疗的HLA-A*02:01+成人mUM患者的护理标准。
方法：使用基于倾向评分的治疗加权逆概率（IPTW）调整分析，平衡年龄，性别,基线乳酸脱氢酶（LDH），基线碱性磷酸酶，疾病位置,ECOG状态,以及从初次诊断到转移的时间。使用IPT加权Kaplan-Meier和Cox比例风险模型评估OS。使用替代缺失数据和权重方法进行敏感性分析。
结果：主要IPTW分析包括来自IMCgp100-202的随机接受tebentafusp的252名患者中的240名和来自GEM-1402的52名纳武单抗联合ipilimumab治疗的患者中的45名。关键基线协变量，包括LDH在加权之前通常平衡良好。IPTW调整后的操作系统支持tebentafusp，HR0.52（95%置信区间[CI]：0.35，0.78）；tebentafusp的1年OS为73%，N+I为50%。敏感性分析显示，所有IPTWHR≤0.61的tebentafusp具有一致的优异OS。pembrolizumab与N+I的IPTW分析显示OS无显著差异(HR0.72;95%CI:0.50,1.06)。
结论：Tebentafusp先前被证明在未经治疗的mUM中与检查点抑制剂或化疗相比具有OS益处。倾向评分分析表明，与NI相比，tebentafusp的OS益处相似。这些数据进一步支持tebentafusp作为先前未治疗的HLA-A*02:01+成人mUM患者的护理标准。
