Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma
Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma
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DOI：
10.1200/jco.2017.75.6270
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发表时间：
2018-06-10
影响因子：
45.3
通讯作者：
Hodi, F. Stephen
中科院分区：
文献类型：
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作者：
Robert, Caroline;Ribas, Antoni;Hodi, F. Stephen
目的Pembrolizumab 对转移性黑色素瘤具有持久的抗肿瘤活性，包括约 15% 的患者完全缓解 (CR)。关于 CR 的潜在预测因素和 CR 后停用派姆单抗后患者处置的数据有限。我们描述了 KEYNOTE-001 研究（ClinicalTrials.gov 标识符：NCT01295827）中使用派姆单抗获得 CR 的患者的基线特征和长期随访。患者和方法未接受伊匹单抗治疗或接受过治疗的晚期/转移性黑色素瘤患者接受了派姆单抗三种剂量方案中的一种。接受 pembrolizumab ≥ 6 个月且至少两次治疗超过确认 CR 的合格患者可以停止治疗。根据实体瘤 1.1 版中的中央疗效评估标准，每 12 周评估一次疗效。对于此分析，根据研究者评估定义 CR，使用单变量和多变量分析评估免疫相关反应标准和 CR 的潜在预测因子。结果 在 655 名接受治疗的患者中，105 名 (16.0%) 在中位随访 43 个月后达到 CR。截至数据截止时，92 名患者 (87.6%) 获得 CR，自首次 CR 起中位随访 30 个月。 14 名 (13.3%) 患者继续接受治疗的中位时间≥ 40 个月。 91 名患者 (86.7%) 停用了派姆单抗，其中 67 名患者 (63.8%) 在没有额外抗癌治疗的情况下继续观察。在所有 105 名 CR 患者中，从 CR 起的 24 个月无病生存率为 90.9%，在 CR 后停止派姆单抗观察的 67 名患者中，该生存率为 89.9%。通过单变量分析，肿瘤大小和程序性死亡配体 1 状态是与 CR 独立相关的基线因素。 结论 转移性黑色素瘤患者在停用派姆单抗后可以获得持久的完全缓解，并且中位随访约 2 年后复发率较低，为一些患者提供了治愈的希望。持久 CR 的机制需要进一步研究。 (c) 2017 年，美国临床肿瘤学会。
PurposePembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study (ClinicalTrials.gov identifier: NCT01295827).Patients and MethodsPatients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for >= 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses.ResultsOf 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of >= 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis.ConclusionPatients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a cure for some patients. The mechanisms underlying durable CR require further investigation. (c) 2017 by American Society of Clinical Oncology.