Caroline Robert, Gustave Roussy Cancer Campus and Paris Sud University, Villejuif Paris-Sud, France; Antoni Ribas, University of California, Los Angeles; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles; Adil Daud, University of California, San Francisco, San Francisco, CA; Jedd D. Wolchok, Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY; Anthony M. Joshua, The Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Wen-Jen Hwu, The University of Texas MD Anderson Cancer Center, Houston; Amita Patnaik, South Texas Accelerated Research Therapeutics, San Antonio, TX; Jeffrey S. Weber, H Lee Moffitt Cancer Center, Tampa; Richard W. Joseph, Mayo Clinic Cancer Center-Florida, Jacksonville, FL; Tara C. Gangadhar, Abramson Cancer Center at the University of Pennsylvania, Philadelphia; Hassane Zarour, UPMC Hillman Cancer Center, Pittsburgh, PA; Roxana Dronca, Mayo Clinic, Rochester, MN; Richard Kefford, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead; Melanoma Institute Australia, Wollstonecraft; and Macquarie University, MQ Health, Health Sciences Centre; Peter Hersey, University of Sydney, Sydney, New South Wales, Australia; Jin Zhang, James Anderson, Scott J. Diede, and Scot Ebbinghaus, Merck & Co., Inc., Kenilworth, NJ; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA.
J Clin Oncol. 2018 Jun 10;36(17):1668-1674. doi: 10.1200/JCO.2017.75.6270. Epub 2017 Dec 28.
Purpose Pembrolizumab 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 Methods Patients 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. Results Of 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. Conclusion Patients 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.
帕博利珠单抗在转移性黑色素瘤中提供持久的抗肿瘤活性，包括约 15%的患者出现完全缓解（CR）。关于 CR 的潜在预测因素以及 CR 后停止使用帕博利珠单抗后患者的处置的数据有限。我们描述了在 KEYNOTE-001 研究（ClinicalTrials.gov 标识符：NCT01295827）中接受帕博利珠单抗治疗后出现 CR 的患者的基线特征和长期随访结果。
未经伊匹单抗治疗或经伊匹单抗治疗的晚期/转移性黑色素瘤患者接受三种帕博利珠单抗剂量方案之一的治疗。接受帕博利珠单抗治疗至少 6 个月且在确认 CR 后至少接受两次治疗的合格患者可以停止治疗。通过中央实体瘤反应评估标准 1.1 每 12 周评估一次反应。在这项分析中，根据研究者评估、免疫相关反应标准和 CR 的潜在预测因素来定义 CR，并使用单变量和多变量分析进行评估。
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。在数据截止时，92 名（87.6%）患者出现 CR，从首次 CR 开始的中位随访时间为 30 个月。14 名（13.3%）患者继续接受治疗，中位时间≥40 个月。91 名（86.7%）患者停止使用帕博利珠单抗治疗，包括 67 名（63.8%）患者在没有额外抗癌治疗的情况下继续观察。所有 105 名 CR 患者的 24 个月无疾病生存率为 90.9%，67 名在 CR 后停止使用帕博利珠单抗进行观察的患者的 24 个月无疾病生存率为 89.9%。肿瘤大小和程序性死亡配体 1 状态是单变量分析中与 CR 独立相关的基线因素之一。
转移性黑色素瘤患者在停止使用帕博利珠单抗后可获得持久的完全缓解，并且从停止治疗后约 2 年的中位随访期复发率较低，为一些患者带来了治愈的希望。持久 CR 的机制需要进一步研究。
