Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Department of Medicine, Blacktown Hospital, Blacktown, New South Wales, Australia.
Clin Cancer Res. 2020 Oct 1;26(19):5086-5091. doi: 10.1158/1078-0432.CCR-20-0177. Epub 2020 Jun 30.
Combination therapy with reduced-dose programmed death 1 inhibitor plus standard-dose cytotoxic T-lymphocyte-associated antigen 4 inhibitor demonstrated efficacy, but substantial toxicity, in melanoma. We present long-term results of part 1B of KEYNOTE-029, which assessed safety and efficacy of standard-dose pembrolizumab plus reduced-dose ipilimumab in advanced melanoma.
Part 1B was an expansion cohort of the open-label, phase Ib portion of KEYNOTE-029. Eligible patients had advanced melanoma and no previous immune checkpoint inhibitor therapy. Patients received pembrolizumab 2 mg/kg (amended to 200 mg) every 3 weeks plus ipilimumab 1 mg/kg every 3 weeks (four cycles), then pembrolizumab alone for up to 2 years. Primary end point was safety; secondary end points included objective response rate (ORR), progression-free survival (PFS), duration of response (DOR), and overall survival (OS).
A total of 153 patients received at least one dose of pembrolizumab plus ipilimumab. At a median follow-up of 36.8 months, 71.9% had received four doses of ipilimumab and 30.7% had completed 2 years of pembrolizumab; 26.1% completed both treatments. Treatment-related adverse events occurred in 96.1% (47.1% grade 3/4; no deaths), leading to discontinuation of one or both study drugs in 35.9%. ORR was 62.1% with 42 (27.5%) complete and 53 (34.6%) partial responses. Median DOR was not reached; 36-month ongoing response rate was 84.2%. Median PFS and OS were not reached; 36-month rates were 59.1% and 73.4%, respectively.
Standard-dose pembrolizumab plus reduced-dose ipilimumab demonstrated robust antitumor activity, durable response, and favorable long-term survival with manageable toxicity.
在黑色素瘤中，与标准剂量细胞毒性 T 淋巴细胞相关抗原 4 抑制剂联合使用的低剂量程序性死亡 1 抑制剂联合疗法显示出疗效，但毒性较大。我们报告 KEYNOTE-029 研究的 1B 部分的长期结果，该研究评估了晚期黑色素瘤患者中标准剂量的 pembrolizumab 联合低剂量 ipilimumab 的安全性和疗效。
1B 部分是 KEYNOTE-029 的开放性、Ib 期部分的扩展队列。符合条件的患者患有晚期黑色素瘤且以前未接受过免疫检查点抑制剂治疗。患者每 3 周接受 pembrolizumab 2mg/kg（修订为 200mg）联合 ipilimumab 1mg/kg（每 3 周 4 个周期），然后单独使用 pembrolizumab 长达 2 年。主要终点为安全性；次要终点包括客观缓解率（ORR）、无进展生存期（PFS）、缓解持续时间（DOR）和总生存期（OS）。
共有 153 名患者接受了至少一剂 pembrolizumab 联合 ipilimumab 治疗。中位随访 36.8 个月时，71.9%的患者接受了 4 剂 ipilimumab，30.7%的患者完成了 2 年的 pembrolizumab 治疗；26.1%的患者完成了两种治疗。治疗相关不良事件发生率为 96.1%（47.1%为 3/4 级；无死亡），导致 35.9%的患者停止使用一种或两种研究药物。ORR 为 62.1%，完全缓解 42 例（27.5%），部分缓解 53 例（34.6%）。中位 DOR 未达到；36 个月时的持续缓解率为 84.2%。中位 PFS 和 OS 未达到；36 个月时的发生率分别为 59.1%和 73.4%。
标准剂量 pembrolizumab 联合低剂量 ipilimumab 显示出强大的抗肿瘤活性、持久的缓解和良好的长期生存，毒性可管理。
