Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.
Sun Yat-sen University, Guangzhou, China.
Clin Cancer Res. 2020 Aug 15;26(16):4250-4259. doi: 10.1158/1078-0432.CCR-19-3922. Epub 2020 Apr 22.
In contrast to the predominant chronic UV exposure-induced cutaneous melanoma in Caucasians, acral and mucosal comprise the majority of melanomas in Asia and respond less effectively to established treatments. The clinical application of PD-1 blockade is yet to be explored in metastatic melanoma in China.
This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese patients with melanoma who had failed in systemic treatments. Toripalimab was given at 3 mg/kg i.v. once every 2 weeks until disease progression or unacceptable toxicity. The primary objective was safety and objective response rate.
128 Patients with melanoma were enrolled, including 50 acral and 22 mucosal. As of August 15, 2019, 23 months after the last enrollment, 116 (90.6%) experienced treatment-related adverse events. ≥Grade 3 TRAEs occurred in 25 (19.5%) patients. Among 127 patients assessed, 1 complete response, 21 partial response, and 51 stable disease were observed for objective response rate of 17.3% and disease control rate of 57.5%. Median duration of response was not reached. Median progression-free survival was 3.6 months [95% confidence interval (CI) 2.7-5.3] and median overall survival was 22.2 months (95% CI, 15.3-NE). Patients with positive PD-L1 staining in tumor biopsies had significant better ORR (38.5% vs. 11.9%, = 0.0065), PFS (7.7 months vs. 2.7 months, = 0.013), and OS (not reached vs. 14.4 months, = 0.0005) than PD-L1-negative patients.
This is the largest prospective anti-PD-1 clinical study in advanced melanoma with predominantly acral and mucosal subtypes. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma refractory to standard therapy..
与白种人主要由慢性紫外线暴露引起的皮肤黑色素瘤相反，肢端和黏膜黑色素瘤构成了亚洲黑色素瘤的大多数，对已建立的治疗方法反应效果较差。PD-1 阻断剂在中国大陆转移性黑色素瘤中的临床应用尚未得到探索。
这项 II 期研究旨在评估特瑞普利单抗在已接受系统治疗失败的中国晚期黑色素瘤患者中的安全性和疗效。特瑞普利单抗以 3mg/kg 静脉输注，每 2 周一次，直至疾病进展或不可接受的毒性。主要目的是安全性和客观缓解率。
共纳入 128 例黑色素瘤患者，其中肢端 50 例，黏膜 22 例。截至 2019 年 8 月 15 日，最后一次入组后 23 个月，116 例（90.6%）患者发生与治疗相关的不良事件。25 例（19.5%）患者发生≥3 级 TRAE。在 127 例可评估的患者中，观察到 1 例完全缓解，21 例部分缓解和 51 例疾病稳定，客观缓解率为 17.3%，疾病控制率为 57.5%。中位缓解持续时间未达到。中位无进展生存期为 3.6 个月（95%CI 2.7-5.3），中位总生存期为 22.2 个月（95%CI 15.3-NE）。肿瘤活检中 PD-L1 染色阳性的患者具有显著更好的 ORR（38.5%比 11.9%，=0.0065）、PFS（7.7 个月比 2.7 个月，=0.013）和 OS（未达到比 14.4 个月，=0.0005）。
这是最大的针对肢端和黏膜为主的晚期黑色素瘤的抗 PD-1 前瞻性临床研究。特瑞普利单抗在中国转移性黑色素瘤患者中显示出可管理的安全性和持久的临床反应，这些患者对标准治疗耐药。
