Long-term Follow-up of Standard-Dose Pembrolizumab Plus Reduced-Dose Ipilimumab in Patients with Advanced Melanoma: KEYNOTE-029 Part 1B
Long-term Follow-up of Standard-Dose Pembrolizumab Plus Reduced-Dose Ipilimumab in Patients with Advanced Melanoma: KEYNOTE-029 Part 1B
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DOI：
10.1158/1078-0432.ccr-20-0177
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发表时间：
2020-10-01
影响因子：
11.5
通讯作者：
Long, Georgina, V
中科院分区：
文献类型：
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作者：
Carlino, Matteo S.;Menzies, Alexander M.;Long, Georgina, V
目的：减少剂量的程序性死亡 1 抑制剂加标准剂量的细胞毒性 T 淋巴细胞相关抗原 4 抑制剂的联合治疗在黑色素瘤中显示出疗效，但具有显着的毒性。我们介绍了 KEYNOTE-029 第 1B 部分的长期结果，该结果评估了标准剂量派姆单抗加减量伊匹单抗治疗晚期黑色素瘤的安全性和有效性。 患者和方法：第 1B 部分是 KEYNOTE-029 开放标签 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既往未接受免疫检查点抑制剂治疗。患者每 3 周接受 2 mg/kg 派姆单抗（修改为 200 mg）加每 3 周 1 mg/kg 伊匹单抗（四个周期），然后单独接受派姆单抗长达 2 年。主要终点是安全性；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)。 结果：总共 153 名患者接受了至少一剂派姆单抗加伊匹单抗治疗。在中位随访时间为 36.8 个月时，71.9% 的患者已接受四剂易普利姆玛治疗，30.7% 的患者已完成 2 年的派姆单抗治疗； 26.1% 完成了两种治疗。 96.1% 的患者发生了治疗相关的不良事件（47.1% 为 3/4 级；无死亡），导致 35.9% 的患者停用一种或两种研究药物。 ORR 为 62.1%，其中 42 例 (27.5%) 完全缓解，53 例 (34.6%) 部分缓解。未达到中位 DOR； 36 个月持续缓解率为 84.2%。未达到中位 PFS 和 OS； 36 个月的发生率分别为 59.1% 和 73.4%。 结论：标准剂量派姆单抗加减量易普利姆玛显示出强大的抗肿瘤活性、持久的反应和良好的长期生存率，且毒性可控。
Purpose: 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.Patients and Methods: 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).Results: 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.Conclusions: Standard-dose pembrolizumab plus reduceddose ipilimumab demonstrated robust antitumor activity, durable response, and favorable long-term survival with manageable toxicity.