Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥ 1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial
Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥ 1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial
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DOI：
10.1186/s40425-017-0310-x
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发表时间：
2018-01-19
影响因子：
10.9
通讯作者：
Nghiem, Paul
中科院分区：
文献类型：
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作者：
Kaufman, Howard L.;Russell, Jeffery S.;Nghiem, Paul
背景资料：默克尔细胞癌（MCC）是一种罕见的侵袭性皮肤癌，与远处转移性疾病（mMCC）患者的生存结局较差相关。在JAVELIN默克尔200（一项针对mMCC的II期、前瞻性、开放标签、单组试验）的初步分析中，avelumab（一种人源抗程序性死亡配体1（PD-L1）单克隆抗体）显示出有前景的疗效和安全性特征，通常可管理和耐受。在这里，我们报告了avelumab的疗效后>= 1年的随访，在远处mMCC的患者，已取得进展后，先前化疗的转移性diseases.Patients和方法：患者接受avelumab 10 mg/kg的1小时静脉输注，每2周，直到确认的疾病进展，不可接受的毒性，或退出。主要终点为最佳总体缓解。次要终点包括反应持续时间（DOR），无进展生存期（PFS）和总生存期（OS）。确认的客观缓解率为33。0%（95% CI，23.3%-43.8%;完全缓解：11.4%）。估计74%的回复持续时间>= 1年，72.4%的回复在数据截止时仍在进行中。反应是持久的，中位DOR尚未达到（95%CI，18。0个月-无法估计），PFS延长; 1年PFS和OS率分别为30%（95% CI，21%-41%）和52%（95% CI，41%-62%）。中位OS为12.9个月（95% CI，7.5-无法估计）。亚组分析表明，既往接受系统治疗线较少、基线疾病负荷较低和PD-L1阳性肿瘤患者的缓解概率较高;然而，无论基线因素如何，包括肿瘤默克尔细胞多瘤病毒状态，均发生持久缓解。随着随访时间的延长，avelumab在化疗后疾病进展的远处mMCC患者中继续显示出持久的缓解和有希望的生存结局。
Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after >= 1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease.Patients and methods: Patients received avelumab 10 mg/kg by 1-h intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was best overall response. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).Results: Patients (N = 88) were followed for a minimum of 12 months. The confirmed objective response rate was 33. 0% (95% CI, 23.3%-43.8%; complete response: 11.4%). An estimated 74% of responses lasted >= 1 year, and 72.4% of responses were ongoing at data cutoff. Responses were durable, with the median DOR not yet reached (95% CI, 18. 0 months-not estimable), and PFS was prolonged; 1-year PFS and OS rates were 30% (95% CI, 21%-41%) and 52% (95% CI, 41%-62%), respectively. Median OS was 12.9 months (95% CI, 7.5-not estimable). Subgroup analyses suggested a higher probability of response in patients receiving fewer prior lines of systemic therapy, with a lower baseline disease burden, and with PD-L1-positive tumors; however, durable responses occurred irrespective of baseline factors, including tumor Merkel cell polyomavirus status.Conclusions: With longer follow-up, avelumab continues to show durable responses and promising survival outcomes in patients with distant mMCC whose disease had progressed after chemotherapy.