PDF(Pubmed)
Abstract：
BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and aggressive neoplasm. We still lack effective treatment options, so survival rates remain very low. Here, we aimed to evaluate the activity of the combination of lenvatinib and pembrolizumab as systemic first-line therapy in ATC.
METHODS: In a retrospective analysis, we investigated the activity and tolerability of combined lenvatinib (starting dose 14 to 24 mg daily) and pembrolizumab (200 mg every three weeks) as first-line therapy in an institutional cohort of ATC patients.
RESULTS: Five patients with metastatic ATC received lenvatinib and pembrolizumab as systemic first-line therapy. The median progression-free survival was 4.7 (range 0.8-5.9) months, and the median overall survival was 6.3 (range 0.8-not reached) months. At the first follow-up, one patient had partial response, three patients had stable disease, and one patient was formally not evaluable due to interference of assessment by concomitant acute infectious thyroiditis. This patient was then stable for more than one year and was still on therapy at the data cutoff without disease progression. Further analyses revealed deficient DNA mismatch repair, high CD8+ lymphocyte infiltration, and low macrophage infiltration in this patient. Of the other patients, two had progressive disease after adverse drug reactions and therapy de-escalation, and two died after the first staging. For all patients, the PD-L1 combined positive score ranged from 12 to 100%.
CONCLUSIONS: The combination of lenvatinib and pembrolizumab was effective and moderately tolerated in treatment-naïve ATC patients with occasional long-lasting response. However, we could not confirm the exceptional responses for this combination therapy reported before in pretreated patients.
METHODS: In a retrospective analysis, we investigated the activity and tolerability of combined lenvatinib (starting dose 14 to 24 mg daily) and pembrolizumab (200 mg every three weeks) as first-line therapy in an institutional cohort of ATC patients.
RESULTS: Five patients with metastatic ATC received lenvatinib and pembrolizumab as systemic first-line therapy. The median progression-free survival was 4.7 (range 0.8-5.9) months, and the median overall survival was 6.3 (range 0.8-not reached) months. At the first follow-up, one patient had partial response, three patients had stable disease, and one patient was formally not evaluable due to interference of assessment by concomitant acute infectious thyroiditis. This patient was then stable for more than one year and was still on therapy at the data cutoff without disease progression. Further analyses revealed deficient DNA mismatch repair, high CD8+ lymphocyte infiltration, and low macrophage infiltration in this patient. Of the other patients, two had progressive disease after adverse drug reactions and therapy de-escalation, and two died after the first staging. For all patients, the PD-L1 combined positive score ranged from 12 to 100%.
CONCLUSIONS: The combination of lenvatinib and pembrolizumab was effective and moderately tolerated in treatment-naïve ATC patients with occasional long-lasting response. However, we could not confirm the exceptional responses for this combination therapy reported before in pretreated patients.
摘要：
背景：间变性甲状腺癌（ATC）是一种罕见的侵袭性肿瘤。我们仍然缺乏有效的治疗选择，所以存活率仍然很低。这里,我们旨在评估乐伐替尼和派博利珠单抗联合作为ATC系统一线治疗的活性.
方法：在回顾性分析中，在ATC患者的机构队列中,我们调查了lenvatinib(起始剂量为每日14~24mg)和pembrolizumab(每3周200mg)作为一线治疗的活性和耐受性.
结果：5例转移性ATC患者接受了lenvatinib和pembrolizumab作为全身一线治疗。中位无进展生存期为4.7（范围0.8-5.9）个月，中位总生存期为6.3个月(范围0.8-未达到).在第一次随访时，一名患者有部分反应，三名患者病情稳定，1例患者由于伴随急性感染性甲状腺炎对评估的干扰而无法正式评估.然后，该患者稳定了一年以上，并且在数据截止时仍在接受治疗，没有疾病进展。进一步的分析显示缺乏DNA错配修复，高CD8+淋巴细胞浸润，这个病人的巨噬细胞浸润低。在其他病人中，两个人在药物不良反应和治疗降级后病情进展，两人在第一次演出后死亡。对于所有患者来说，PD-L1联合阳性评分为12%~100%.
结论：lenvatinib和pembrolizumab的组合在治疗初期的ATC患者中是有效的，并且具有中等的耐受性，偶尔有长期的反应。然而,我们无法确认之前报道的这种联合治疗在预处理患者中的异常缓解.
方法：在回顾性分析中，在ATC患者的机构队列中,我们调查了lenvatinib(起始剂量为每日14~24mg)和pembrolizumab(每3周200mg)作为一线治疗的活性和耐受性.
结果：5例转移性ATC患者接受了lenvatinib和pembrolizumab作为全身一线治疗。中位无进展生存期为4.7（范围0.8-5.9）个月，中位总生存期为6.3个月(范围0.8-未达到).在第一次随访时，一名患者有部分反应，三名患者病情稳定，1例患者由于伴随急性感染性甲状腺炎对评估的干扰而无法正式评估.然后，该患者稳定了一年以上，并且在数据截止时仍在接受治疗，没有疾病进展。进一步的分析显示缺乏DNA错配修复，高CD8+淋巴细胞浸润，这个病人的巨噬细胞浸润低。在其他病人中，两个人在药物不良反应和治疗降级后病情进展，两人在第一次演出后死亡。对于所有患者来说，PD-L1联合阳性评分为12%~100%.
结论：lenvatinib和pembrolizumab的组合在治疗初期的ATC患者中是有效的，并且具有中等的耐受性，偶尔有长期的反应。然而,我们无法确认之前报道的这种联合治疗在预处理患者中的异常缓解.
