Sherman Eric J, Dunn Lara A, Ho Alan L, Baxi Shrujal S, Ghossein Ronald A, Fury Matthew G, Haque Sofia, Sima Cami S, Cullen Grace, Fagin James A, Pfister David G
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Department of Medicine, Weill Cornell Medicine, New York, New York.
Cancer. 2017 Nov 1;123(21):4114-4121. doi: 10.1002/cncr.30861. Epub 2017 Jun 29.
Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results.
In this single-institution, phase 2 study, 36 patients with metastatic, radioactive iodine-refractory thyroid carcinoma of follicular origin received treatment with the combination of oral sorafenib (200 mg twice daily) and intravenous temsirolimus (25 mg weekly). The receipt of prior systemic treatment with cytotoxic chemotherapy and targeted therapy, including sorafenib, was permitted. The primary endpoint was the radiographic response rate.
The best response was a partial response in 8 patients (22%), stable disease in 21 (58%), and progressive disease in 1 (3%). Six patients were not evaluable for a response. Patients who had received any prior systemic treatment had a response rate of 10% compared with 38% of those who had not received prior systemic treatment. One of 2 patients with anaplastic thyroid cancer had an objective response. The progression-free survival rate at 1 year was 30.5%. The most common grade 3 and 4 toxicities associated with sorafenib and temsirolimus included hyperglycemia, fatigue, anemia, and oral mucositis.
Sorafenib and temsirolimus appear to be an active combination in patients with radioactive iodine-refractory thyroid carcinoma, especially in patients who received no prior treatment compared with historic data from single-agent sorafenib. Activity is also observed in patients who previously received sorafenib. This regimen warrants further investigation. Cancer 2017;123:4114-4121. © 2017 American Cancer Society.
复发性和/或转移性放射性碘难治性甲状腺癌患者的治疗选择有限。索拉非尼是一种口服激酶抑制剂，已被美国食品药品监督管理局批准用于治疗放射性碘难治性甲状腺癌，尽管在一线治疗中作为单药使用时其缓解率较低（12.2%）。本研究的目的是确定在索拉非尼中添加雷帕霉素靶蛋白抑制剂替西罗莫司是否能改善这些结果。
在这项单机构2期研究中，36例滤泡源性转移性放射性碘难治性甲状腺癌患者接受了口服索拉非尼（每日2次，每次200 mg）和静脉注射替西罗莫司（每周25 mg）联合治疗。允许患者之前接受过细胞毒性化疗和靶向治疗，包括索拉非尼。主要终点是影像学缓解率。
最佳缓解为8例患者部分缓解（22%），21例病情稳定（58%），1例疾病进展（3%）。6例患者无法评估缓解情况。接受过任何先前全身治疗的患者缓解率为10%，而未接受过先前全身治疗的患者缓解率为38%。2例间变性甲状腺癌患者中有1例出现客观缓解。1年无进展生存率为30.5%。与索拉非尼和替西罗莫司相关的最常见3级和4级毒性包括高血糖、疲劳、贫血和口腔黏膜炎。
与单药索拉非尼的历史数据相比，索拉非尼和替西罗莫司联合似乎对放射性碘难治性甲状腺癌患者有效，尤其是未接受过先前治疗的患者。在先前接受过索拉非尼治疗的患者中也观察到了活性。该方案值得进一步研究。《癌症》2017年；123:4114 - 4121。©2017美国癌症协会
