Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma
Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma
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DOI：
10.1200/jco.2016.67.2477
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发表时间：
2016-12-01
影响因子：
45.3
通讯作者：
Hamid, Omid
中科院分区：
文献类型：
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作者：
Daud, Adil I.;Wolchok, Jedd D.;Hamid, Omid
目的程序性死亡配体1（PD-L1）的表达是抗程序性死亡配体1（PD-1）治疗后反应和预后的潜在预测指标。本研究探讨了在Ib期KEYNOTE-001研究（临床试验信息：NCT 01295827）中接受帕博利珠单抗治疗的晚期黑色素瘤患者中抗PD-1活性和PD-L1表达之间的关系。根据实体瘤疗效评价标准（RECIST）v1.1，由独立中心审查每12周评估一次肿瘤缓解。主要结局为客观缓解率。次要结局包括无进展生存期（PFS）和总生存期（OS）。通过临床试验免疫组织化学测定评估肿瘤和肿瘤相关免疫细胞中的膜PD-L1表达（22 C3抗体），并由对临床结果不知情的三名病理学家之一在0至5的独特黑素瘤（MEL）量表上评分;得分>= 2结果在451例具有可评估的PD-L1表达的患者中，344例（76%）为PD-L1阳性肿瘤。人口统计学和分期变量在PD-L1阳性和阴性患者中均匀分布。观察到MEL评分越高，缓解率越高，PFS（风险比，0.76; 95%CI，0.71 - 0.82）和OS（风险比，0.76; 95%CI，0.69 - 0.83）越长（均P <0.001）。MEL 0、1、2、3、4和5的客观缓解率分别为8%、12%、22%、43%、57%和53%.ConclusionPD-L1在预处理肿瘤活检样本中的表达与缓解率、PFS和OS相关;然而，PD-L1阴性肿瘤患者也可能获得持久缓解。(C)2016年美国临床肿瘤学会
PurposeExpression of programmed death-ligand 1 (PD-L1) is a potential predictive marker for response and outcome after treatment with anti-programmed death 1 (PD-1). This study explored the relationship between anti-PD-1 activity and PD-L1 expression in patients with advanced melanoma who were treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827).Patients and MethodsSix hundred fifty-five patients received pembrolizumab10 mg/kg once every 2 weeks or once every 3 weeks, or 2 mg/kg once every 3 weeks. Tumor response was assessed every 12 weeks per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent central review. Primary outcome was objective response rate. Secondary outcomes included progression-free survival (PFS) and overall survival (OS). Membranous PD-L1 expression in tumor and tumor-associated immune cells was assessed by a clinical trial immunohistochemistry assay (22C3 antibody) and scored on a unique melanoma (MEL) scale of 0 to 5 by one of three pathologists who were blinded to clinical outcome; a score >= 2 (membranous staining in >= 1% of cells) was considered positive.ResultsOf 451 patients with evaluable PD-L1 expression, 344 (76%) had PD-L1-positive tumors. Demographic and staging variables were equally distributed among PD-L1-positive and -negative patients. An association between higher MEL score and higher response rate and longer PFS (hazard ratio, 0.76; 95% CI, 0.71 to 0.82) and OS (hazard ratio, 0.76; 95% CI, 0.69 to 0.83) was observed (P < .001 for each). Objective response rate was 8%, 12%, 22%, 43%, 57%, and 53% for MEL 0, 1, 2, 3, 4, and 5, respectively.ConclusionPD-L1 expression in pretreatment tumor biopsy samples was correlated with response rate, PFS, and OS; however, patients with PD-L1-negative tumors may also achieve durable responses. (C) 2016 by American Society of Clinical Oncology