Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
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DOI：
10.1200/jco.2015.64.8931
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发表时间：
2016-07-20
影响因子：
45.3
通讯作者：
Buisseret, Laurence
中科院分区：
文献类型：
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作者：
Nanda, Rita;Chow, Laura Q. M.;Buisseret, Laurence
目的免疫检查点抑制已被证明是一种有效的抗癌策略。几条证据支持三阴性乳腺癌（TNBC）的免疫治疗研究。我们评估了程序性细胞死亡蛋白1（PD-1）抑制剂派姆单抗在晚期TNBC患者中的安全性和抗肿瘤活性。（ClinicalTrials.gov标识符：NCT 01848834）是一项多中心研究，在晚期PD-L1阳性患者中进行的帕博利珠单抗单药静脉给药（10 mg/kg，每2周一次）的非随机化Ib期试验（通过免疫组织化学在基质或1%的肿瘤细胞中表达）TNBC、胃癌、尿路上皮癌和头颈癌。本报告侧重于TNBC cohol.ResultsAmong 111例TNBC患者的肿瘤样本进行了筛选PD-L1表达，58.6%的PD-L1阳性肿瘤。32名女性（中位年龄50.5岁;范围29 - 72岁）入组并评估安全性和抗肿瘤活性。中位给药次数为5次（范围：1 - 36次）。常见毒性为轻度，与其他肿瘤队列中观察到的毒性相似（如关节痛、疲乏、肌痛和恶心），包括5例（15.6%）3级毒性和1例治疗相关死亡患者。在27例可评价抗肿瘤活性的患者中，总有效率为18.5%，中位缓解时间为17.9周（范围，7.3至32.4周），尚未达到中位缓解持续时间（范围、15.0至47.3周）结论本Ib期研究描述了帕博利珠单抗每2周给药一次的临床活性和潜在可接受的安全性特征的初步证据。预处理的晚期TNBC。一项单药II期研究正在进行中，研究的剂量为200 mg，每3周一次（ClinicalTrials.gov标识符：NCT 02447003）。(C)2016年美国临床肿瘤学会
PurposeImmune checkpoint inhibition has been demonstrated to be an effective anticancer strategy. Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab in patients with advanced TNBC.MethodsKEYNOTE-012 (ClinicalTrials.gov identifier: NCT01848834) was a multicenter, nonrandomized phase Ib trial of single-agent pembrolizumab given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD-L1-positive (expression in stroma or 1% of tumor cells by immunohistochemistry) TNBC, gastric cancer, urothelial cancer, and head and neck cancer. This report focuses on the TNBC cohort.ResultsAmong 111 patients with TNBC whose tumor samples were screened for PD-L1 expression, 58.6% had PD-L1-positive tumors. Thirty-two women (median age, 50.5 years; range, 29 to 72 years) were enrolled and assessed for safety and antitumor activity. The median number of doses administered was five (range, 1 to 36 doses). Common toxicities were mild and similar to those observed in other tumor cohorts (eg, arthralgia, fatigue, myalgia, and nausea), and included five (15.6%) patients with grade 3 toxicity and one treatment-related death. Among the 27 patients who were evaluable for antitumor activity, the overall response rate was 18.5%, the median time to response was 17.9 weeks (range, 7.3 to 32.4 weeks), and the median duration of response was not yet reached (range, 15.0 to 47.3 weeks).ConclusionThis phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced TNBC. A single-agent phase II study examining a 200-mg dose given once every 3 weeks (ClinicalTrials.gov identifier: NCT02447003) is ongoing. (C) 2016 by American Society of Clinical Oncology