Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma
Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma
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派姆单抗治疗晚期唾液腺癌
DOI：
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
B. Keam
中科院分区：
文献类型：
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作者：
R. Cohen;J. Delord;T. Doi;S. Piha;Stephen V. Liu;J. Gilbert;A. Algazi;S. Damian;R. Hong;C. le Tourneau;D. Day;A. Varga;E. Élez;J. Wallmark;S. Saraf;Pradeep Thanigaimani;Jonathan D. Cheng;B. Keam
目的：不可切除或转移性涎腺癌（SGC）患者的治疗选择有限。探索了帕博利珠单抗对表达程序性死亡配体1（PD-L1）的SGC的安全性和疗效。材料与方法：在PD-L1阳性晚期实体瘤患者中进行的帕博利珠单抗非随机、多队列、Ib期试验（KEYNOTE-028; NCT 02054806）中入组了一组晚期PD-L1阳性SGC患者。关键入选标准包括复发性或转移性疾病、既往全身治疗失败和≥1%的肿瘤或基质细胞表达PD-L1（根据原型免疫组织化学测定）。患者接受帕博利珠单抗10 mg/kg，每2周一次，持续≥2年或直至确认疾病进展或不可接受的毒性。主要终点是研究者审查的实体瘤疗效评价标准第1.1版的客观缓解率。结果如下：26例PD-L1阳性SGC患者入组并接受治疗;中位年龄为57岁，88%为男性，74%既往接受过复发/转移性疾病治疗。中位随访20个月后确认的客观缓解率为12%（95%置信区间，2%-30%），3例患者达到部分缓解;无完全缓解。中位缓解持续时间为4个月（范围：4至21个月）。22例患者（85%）发生了治疗相关不良事件，导致2例患者停药，1例患者死亡（间质性肺病）; ≥15%的患者发生的不良事件包括腹泻、食欲下降、瘙痒和疲劳。结论：Pembrolizumab在晚期PD-L1阳性SGC患者中表现出有希望的抗肿瘤活性和可管理的安全性特征。
Objectives: Treatment options for patients with unresectable or metastatic salivary gland carcinoma (SGC) are limited. Safety and efficacy of pembrolizumab for SGC expressing programmed death ligand 1 (PD-L1) were explored. Materials and Methods: A cohort of patients with advanced, PD-L1-positive SGC was enrolled in the nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors (KEYNOTE-028; NCT02054806). Key inclusion criteria included recurrent or metastatic disease, failure of prior systemic therapy, and PD-L1 expression on ≥1% of tumor or stroma cells (per a prototype immunohistochemistry assay). Patients received pembrolizumab 10 mg/kg every 2 weeks for ≥2 years or until confirmed disease progression or unacceptable toxicity. Primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator review. Results: Twenty-six patients with PD-L1-positive SGC were enrolled and treated; median age was 57 years, 88% were men, and 74% had received prior therapy for recurrent/metastatic disease. Confirmed objective response rate after median follow-up of 20 months was 12% (95% confidence interval, 2%-30%), with 3 patients achieving partial response; there were no complete responses. Median duration of response was 4 months (range, 4 to 21 mo). Treatment-related adverse events occurred in 22 patients (85%), resulting in discontinuation in 2 patients and death in 1 (interstitial lung disease); those occurring in ≥15% of patients were diarrhea, decreased appetite, pruritus, and fatigue. Conclusions: Pembrolizumab demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, PD-L1-positive SGC.