Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial.
Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial.
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DOI：
10.1016/s1470-2045(19)30728-4
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发表时间：
2020-02
期刊：
影响因子：
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通讯作者：
Rischin D
中科院分区：
文献类型：
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作者：
Migden MR;Khushalani NI;Chang ALS;Lewis KD;Schmults CD;Hernandez-Aya L;Meier F;Schadendorf D;Guminski A;Hauschild A;Wong DJ;Daniels GA;Berking C;Jankovic V;Stankevich E;Booth J;Li S;Weinreich DM;Yancopoulos GD;Lowy I;Fury MG;Rischin D
Cemiplimab在转移性皮肤鳞状细胞癌患者中显示出显著的抗肿瘤活性。局部晚期皮肤鳞状细胞癌患者常规全身治疗预后差。我们提出了cemiplimab在局部晚期皮肤鳞状细胞癌患者中的安全性和抗肿瘤活性的初步分析。这项关键的开放标签、II期、单组试验在澳大利亚、德国和美国的25家门诊诊所（主要是学术医疗中心）进行。合格患者（年龄≥18岁，经组织学证实为局部晚期皮肤鳞状细胞癌，东部肿瘤协作组体能状态评分为0-1）接受cemiplimab 3 mg/kg静脉给药，持续30 min，每2周一次，持续96周。每8周进行一次肿瘤测量。主要终点为客观缓解，定义为根据实体瘤缓解评价标准第1.1版（放射学扫描）和WHO标准（医学摄影），根据独立中心审查获得完全或部分缓解的患者比例。数据截止日期为2018年10月10日，即完全入组队列达到主要分析的预定时间点时。按照意向治疗原则进行分析。安全性分析包括接受至少一剂cemiplimab的所有患者。本研究注册于ClinicalTrials.gov，编号NCT 02760498。2016年6月14日至2018年4月25日期间，78例患者入组并接受cemiplimab治疗。数据截止时，研究随访的中位持续时间为9.3个月（IQR 5.1 - 15.7）。在78例患者中的34例（44%; 95% CI 32-55）中观察到客观缓解。最佳总体缓解为10例（13%）患者完全缓解，24例（31%）患者部分缓解。78例患者中有34例（44%）发生了3-4级治疗后出现的不良事件;最常见的是高血压（6例（8%））和肺炎（4例（5%））。78例患者中有23例（29%）发生了严重的治疗后出现的不良事件。报告了1例治疗相关死亡，发生在吸入性肺炎发作后。Cemiplimab在局部晚期皮肤鳞状细胞癌患者中显示出抗肿瘤活性和可接受的安全性特征，这些患者没有广泛接受的治疗标准。Regeneron制药和赛诺菲。
Cemiplimab has shown substantial antitumour activity in patients with metastatic cutaneous squamous cell carcinoma. Patients with locally advanced cutaneous squamous cell carcinoma have poor prognosis with conventional systemic therapy. We present a primary analysis of the safety and antitumour activity of cemiplimab in patients with locally advanced cutaneous squamous cell carcinoma. This pivotal open-label, phase 2, single-arm trial was done across 25 outpatient clinics, primarily at academic medical centres, in Australia, Germany, and the USA. Eligible patients (aged ≥18 years with histologically confirmed locally advanced cutaneous squamous cell carcinoma and an Eastern Cooperative Oncology Group performance status of 0–1) received cemiplimab 3 mg/kg intravenously over 30 min every 2 weeks for up to 96 weeks. Tumour measurements were done every 8 weeks. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response, according to independent central review as per Response Evaluation Criteria in Solid Tumors version 1.1 for radiological scans and WHO criteria for medical photography. Data cutoff was Oct 10, 2018, when the fully enrolled cohort reached the prespecified timepoint for the primary analysis. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. This study is registered with ClinicalTrials.gov, number NCT02760498. Between June 14, 2016, and April 25, 2018, 78 patients were enrolled and treated with cemiplimab. The median duration of study follow-up was 9·3 months (IQR 5·1–15·7) at the time of data cutoff. An objective response was observed in 34 (44%; 95% CI 32–55) of 78 patients. The best overall response was ten (13%) patients with a complete response and 24 (31%) with a partial response. Grade 3–4 treatment-emergent adverse events occurred in 34 (44%) of 78 patients; the most common were hypertension in six (8%) patients and pneumonia in four (5%). Serious treatment-emergent adverse events occurred in 23 (29%) of 78 patients. One treatment-related death was reported that occurred after onset of aspiration pneumonia. Cemiplimab showed antitumour activity and an acceptable safety profile in patients with locally advanced cutaneous squamous cell carcinoma for whom there was no widely accepted standard of care. Regeneron Pharmaceuticals and Sanofi.