派姆单抗治疗晚期罕见癌症患者的 II 期研究。
Phase 2 study of pembrolizumab in patients with advanced rare cancers.
机构信息
Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
出版信息
J Immunother Cancer. 2020 Mar;8(1). doi: 10.1136/jitc-2019-000347.
BACKGROUND
Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers.
METHODS
In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR).
RESULTS
A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma-pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug.
CONCLUSIONS
The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma-pheochromocytoma supports further evaluation of pembrolizumab in this patient population.
TRIAL REGISTRATION NUMBER
NCT02721732.
背景
晚期罕见癌症患者预后较差，治疗选择有限。由于免疫疗法在多种癌症类型中均有效，我们旨在评估派姆单抗（程序性细胞死亡 1（PD-1）抑制剂）在晚期罕见癌症患者中的疗效。
方法
在这项开放标签、2 期临床试验中，纳入了 9 个肿瘤特异性队列和 1 个用于其他罕见组织学的第 10 个队列的患者，这些患者患有晚期罕见癌症，且在过去 6 个月内，如果有标准治疗方法，其肿瘤已经进展。派姆单抗 200mg 静脉输注，每 21 天 1 次。主要终点为 27 周时的无进展率（NPR）；次要终点为安全性和耐受性、客观缓解率（ORR）和临床获益率（CBR）。
结果
共纳入了 127 例于 2016 年 8 月 15 日至 2018 年 7 月 27 日接受治疗的患者。在数据截止时，27 周时的 NPR 为 28%（95%CI，19%至 37%）。在 110 例可评估患者中，有 15 例（1 例完全缓解，14 例部分缓解）确认有客观缓解（OR）。CBR 定义为 OR 或疾病稳定≥4 个月的患者比例，为 38%（n=42）。在最后一次随访时，15 例有 OR 的患者中有 11 例仍在接受治疗。在皮肤鳞状细胞癌（SCC）队列中，27 周时的 NPR 为 36%，ORR 为 31%，CBR 为 38%。在肾上腺皮质癌（ACC）患者中，27 周时的 NPR 为 31%，ORR 为 15%，CBR 为 54%。在不明原发癌（CUP）患者中，27 周时的 NPR 为 33%，ORR 为 23%，CBR 为 54%。在副神经节瘤-嗜铬细胞瘤队列中，27 周时的 NPR 为 43%，ORR 为 0%，CBR 为 75%。127 例患者中有 66 例（52%）发生了治疗相关不良事件（TRAEs），12 例（9%）发生了≥3 级 TRAEs。最常见的 TRAEs 是疲劳（n=25）和皮疹（n=17）。有 6 例死亡，均与研究药物无关。
结论
皮肤 SCC、ACC、CUP 和副神经节瘤-嗜铬细胞瘤患者中观察到的有利毒性特征和抗肿瘤活性支持进一步评估派姆单抗在这一患者人群中的应用。
临床试验注册号
NCT02721732。
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