KEYNOTE-001 研究中接受派姆单抗治疗的晚期黑色素瘤患者的 5 年生存结果。
Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001.
机构信息
Medical Oncology, The Angeles Clinic and Research Institute, Los Angeles, USA.
Department of Dermatology, Gustave Roussy, Villejuif; Department of Medicine, University of Paris-Sud, Paris, France.
出版信息
Ann Oncol. 2019 Apr 1;30(4):582-588. doi: 10.1093/annonc/mdz011.
BACKGROUND
Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed.
PATIENTS AND METHODS
Patients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017).
RESULTS
KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2-30.4) and 38.6 months (95% CI, 27.2-not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE.
CONCLUSIONS
This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma.
CLINICAL TRIAL REGISTRY
ClinicalTrials.gov, NCT01295827.
背景
帕博利珠单抗在 Ib 期 KEYNOTE-001 研究（NCT01295827）中表现出了强大的抗肿瘤活性和安全性，该研究纳入了晚期黑色素瘤患者。本文报告了所有患者和未经治疗的患者的 5 年结局，并分析了初始应答后疾病进展且接受了第二疗程帕博利珠单抗治疗的患者。
方法
年龄≥18 岁、先前接受过治疗或未经治疗的晚期/转移性黑色素瘤患者接受帕博利珠单抗 2mg/kg，每 3 周 1 次、10mg/kg，每 3 周 1 次或 10mg/kg，每 2 周 1 次，直至疾病进展、无法耐受毒性或患者/研究者决定停药。采用 Kaplan-Meier 法计算总生存期（OS）和无进展生存期（PFS）。根据研究者评估的免疫相关缓解标准（数据截止日期为 2017 年 9 月 1 日），计算客观缓解率和 PFS。
结果
KEYNOTE-001 纳入了 655 例黑色素瘤患者；中位随访时间为 55 个月。所有患者的 5 年 OS 估计值为 34%，未经治疗患者的 5 年 OS 估计值为 41%；中位 OS 分别为 23.8 个月（95%CI，20.2-30.4）和 38.6 个月（95%CI，27.2-未达到）。所有患者的 5 年 PFS 率估计值为 21%，未经治疗患者的 5 年 PFS 率估计值为 29%；中位 PFS 分别为 8.3 个月（95%CI，5.8-11.1）和 16.9 个月（95%CI，9.3-35.5）。中位缓解持续时间未达到；数据截止时，所有缓解的 73%和未经治疗缓解的 82%仍在持续；最长缓解时间为 66 个月。4 例（均为完全缓解（CR）初始应答者）在观察期间疾病进展后接受了第二疗程帕博利珠单抗治疗。各有 1 例患者在数据截止后分别达到 CR 和部分缓解。治疗相关不良事件（TRAEs）发生于 86%的患者，导致 7.8%的患者停药；17%的患者发生 3/4 级 TRAE。
结论
这是 KEYNOTE-001 的 5 年分析，代表了帕博利珠单抗迄今为止最长的随访时间，证实了帕博利珠单抗在晚期黑色素瘤中的持久抗肿瘤活性和耐受性。
临床试验注册
ClinicalTrials.gov，NCT01295827。
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