挽救性靶向治疗在一线索拉非尼治疗失败的分化型甲状腺癌患者中的作用。
Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib.
作者信息
Dadu Ramona, Devine Catherine, Hernandez Mike, Waguespack Steven G, Busaidy Naifa L, Hu Mimi I, Jimenez Camilo, Habra Mouhammad A, Sellin Rena V, Ying Anita K, Cote Gilbert J, Sherman Steven I, Cabanillas Maria E
机构信息
Departments of Endocrine Neoplasia and Hormonal Disorders (R.D., S.G.W., N.L.B., M.I.H., C.J., M.A.H., R.V.S., A.K.Y., G.J.C., S.I.S., M.E.C.), Diagnostic Radiology (C.D.), and Biostatistics (M.H.), The University of Texas M. D. Anderson Cancer Center; and Department of Endocrinology, Diabetes, and Metabolism (R.D.), Baylor College of Medicine, Houston, Texas 77030.
出版信息
J Clin Endocrinol Metab. 2014 Jun;99(6):2086-94. doi: 10.1210/jc.2013-3588. Epub 2014 Mar 14.
CONTEXT
Sorafenib, a tyrosine kinase inhibitor, is a common first-line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem.
OBJECTIVE
The objective of the study was to determine the efficacy of salvage therapy after first-line sorafenib failure.
DESIGN
This was a retrospective review at M. D. Anderson Cancer Center from January 2005 to May 2013.
PATIENTS
The study included patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). PATIENTS who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS).
OUTCOME MEASURES
Progression-free survival, best response, and median OS were measured.
RESULTS
Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients receiving first line sorafenib was 37 months; median OS was significantly longer with salvage therapy compared with sorafenib alone (58 vs 28 months, P = .013). In group 2, 17 patients were evaluable for best response, although two patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response in 2 of 15 (13%), stable disease in 10 of 15 (67%), and progressive disease in 3 of 15 (20%) patients. With salvage therapy, partial responses were seen in 7 of 17 (41%) and stable disease in 10 of 17 (59%) patients. Median progression-free survival was 7.4 months with first-line sorafenib and 11.4 months with salvage therapy. Salvage therapy included sunitinib (n = 4), pazopanib (n = 3), cabozantinib (n = 4), lenvatinib (n = 3), and vemurafenib (n = 3).
CONCLUSIONS
Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.
背景
索拉非尼是一种酪氨酸激酶抑制剂，是晚期分化型甲状腺癌（DTC）常见的一线治疗药物。然而，疗效并不持久，药物毒性仍然是一个问题。
目的
本研究的目的是确定一线索拉非尼治疗失败后挽救治疗的疗效。
设计
这是一项对2005年1月至2013年5月在MD安德森癌症中心进行的回顾性研究。
患者
本研究纳入了转移性DTC患者，这些患者在最初的索拉非尼治疗失败后接受了挽救治疗（第2组）。仅接受一线索拉非尼治疗的患者（第1组）用于评估总生存期（OS）以作比较。
观察指标
测量无进展生存期、最佳反应和中位OS。
结果
纳入64例转移性、放射性碘难治性DTC患者；第1组35例，第2组25例，两组均衡性良好。所有64例接受一线索拉非尼治疗的患者中位OS为37个月；与单纯索拉非尼治疗相比，挽救治疗的中位OS显著更长（58个月对28个月，P = 0.013）。在第2组中，17例患者可评估最佳反应，尽管有2例患者出现索拉非尼毒性，在重新分期前停药。一线索拉非尼治疗的最佳反应为15例中的2例部分缓解（13%），15例中的10例病情稳定（67%），15例中的3例疾病进展（20%）。采用挽救治疗时，17例中的7例出现部分缓解（41%），17例中的10例病情稳定（59%）。一线索拉非尼治疗的中位无进展生存期为7.4个月，挽救治疗为11.4个月。挽救治疗包括舒尼替尼（n = 4）、帕唑帕尼（n = 3）、卡博替尼（n = 4）、乐伐替尼（n = 3）和维莫非尼（n = 3）。
结论
尽管作用机制相似，但其他靶向药物在索拉非尼治疗失败后是有效的挽救治疗方法，应提供给能够接受挽救治疗的患者。
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