Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1461, Houston, TX, 77030, USA.
Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1482, Houston, TX, 77030, USA.
J Immunother Cancer. 2018 Jul 11;6(1):68. doi: 10.1186/s40425-018-0378-y.
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare but deadly form of thyroid cancer. Kinase inhibitors kinase inhibitors have shown clinical efficacy in the management of ATC, however, eventually these tumors acquire resistance to KI and patients succumb to their disease. Salvage therapy in this setting is limited. As ATC tumors diffusely express the programmed cell death protein ligand (PD-L1), anti- programmed cell death protein (PD-1) drugs such as pembrolizumab offer therapeutic potential. We sought to explore the efficacy of adding pembrolizumab to kinase inhibitors at progression in ATC. METHODS: We retrospectively reviewed the charts of ATC patients initiated on pembrolizumab in combination with KI at the time of progression on kinase inhibitors at MD Anderson Cancer Center between August 2016 and August 2017. Efficacy was evaluated with best overall response (BOR) using RECISTv1.1 criteria. Progression free survival (PFS) from the start of pembrolizumab and overall survival (OS) from the start of kinase inhibitors, as well as from the time of addition of pembrolizumab were calculated. RESULTS: Twelve patients were treated with combination kinase inhibitors plus pembrolizumab at the time of progression on their KI therapy. Median age at initiation of pembrolizumab was 60 years (range 47-84 years). BOR was as follows: 5/12 (42%) had partial response, 4/12 (33%) had stable disease and 3/12 (25%) had progressive disease. Median OS from the start of kinase inhibitor was 10.43 months (95% CI = 6.02, 14.83, range 5.4-40 months). Median OS and PFS from the addition of pembrolizumab were 6.93 months (95% CI = 1.7, 12.15, range 3-15.9 months) and 2.96 months (95% CI = 2.2, 3.7, range 0.57-13.14 months), respectively. Fatigue, anemia and hypertension were the most common AEs encountered on these combinations. Therapy had to be discontinued in 2 patients due to drug induced rash and altered mental status likely from progression of disease. CONCLUSION: In a subset of ATC patients, pembrolizumab may be an effective salvage therapy added to kinase inhibitors at the time of progression on these drugs. However, better treatment strategies aimed at incorporating immunotherapy in patients with ATC should be explored. Frontline combination of KI with immunotherapy should be studied in prospective clinical trials.
背景：间变性甲状腺癌（ATC）是一种罕见但致命的甲状腺癌。激酶抑制剂在 ATC 的治疗中显示出临床疗效，然而，这些肿瘤最终会对 KI 产生耐药性，患者会因此而死亡。在这种情况下，挽救性治疗是有限的。由于 ATC 肿瘤广泛表达程序性细胞死亡蛋白配体（PD-L1），因此抗程序性细胞死亡蛋白（PD-1）药物，如 pembrolizumab 具有治疗潜力。我们试图探讨在 ATC 进展时将 pembrolizumab 与激酶抑制剂联合使用的疗效。
方法：我们回顾性分析了 2016 年 8 月至 2017 年 8 月期间在 MD 安德森癌症中心接受 pembrolizumab 联合激酶抑制剂治疗的进展期 ATC 患者的病历。使用 RECISTv1.1 标准评估最佳总体反应（BOR）。从开始使用 pembrolizumab 计算无进展生存期（PFS）和从开始使用激酶抑制剂计算总生存期（OS），以及从开始使用 pembrolizumab 计算总生存期（OS）。
结果：12 名患者在其 KI 治疗进展时接受了联合激酶抑制剂加 pembrolizumab 的治疗。开始使用 pembrolizumab 时的中位年龄为 60 岁（范围为 47-84 岁）。BOR 如下：5/12（42%）有部分缓解，4/12（33%）有稳定疾病，3/12（25%）有进展性疾病。从开始使用激酶抑制剂到中位 OS 为 10.43 个月（95%CI=6.02，14.83，范围 5.4-40 个月）。从加入 pembrolizumab 到中位 OS 和 PFS 分别为 6.93 个月（95%CI=1.7，12.15，范围 3-15.9 个月）和 2.96 个月（95%CI=2.2，3.7，范围 0.57-13.14 个月）。这些组合中最常见的不良事件是疲劳、贫血和高血压。由于药物引起的皮疹和精神状态改变，可能是由于疾病进展，有 2 名患者不得不停止治疗。
结论：在 ATC 患者的亚组中，pembrolizumab 可能是一种有效的挽救性治疗方法，可在这些药物进展时添加激酶抑制剂。然而，应该探索更好的治疗策略，旨在将免疫疗法纳入 ATC 患者。应在前瞻性临床试验中研究 KI 与免疫疗法的一线联合治疗。
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