Remon Jordi, Girard Nicolas, Mazieres Julien, Dansin Eric, Pichon Eric, Greillier Laurent, Dubos Catherine, Lindsay Colin R, Besse Benjamin
Gustave Roussy Cancer Campus, Villejuif, France.
Louis Pradel Hospital, Hospices Civils de Lyon Cancer Institute, Lyon, France.
Lung Cancer. 2016 Jul;97:99-104. doi: 10.1016/j.lungcan.2016.04.024. Epub 2016 May 3.
Sunitinib is a potent oral tyrosine kinase inhibitor of VEGFRs, KIT, and PDGFRs. In a single arm phase II trial, sunitinib has demonstrated its potential activity in refractory thymic carcinoma (TC) and thymoma (T). Taking advantage of the French RYTHMIC network prospective database, we investigated the off-label efficacy of sunitinib in previously-treated thymic epithelial tumors (TETs) patients not included in a clinical trial.
RYTHMIC database started in 2012, and prospectively collects clinical, imaging, treatment, and follow-up data of all patients diagnosed with TET, for whom management is discussed at a national multidisciplinary tumor board. All patients who received sunitinib were selected for this analysis.
28 patients from 7 institutions were identified, including 20 TC and 8T; 32% of patients were females, and median age was 50 years. Fifteen patients (54%) received sunitinib as ≥4th line treatment. The initial daily dose of sunitinib was 50mg in 11 patients, 37.5mg in 16 patients and 25mg in 1 patient. Sunitinib adverse events were all manageable and tolerable; 8 patients had to stop sunitinib due to toxicity after a median duration of treatment of 2.7 months. In the overall population, disease control rate was of 63% (86% for T, and 55% for TC); overall response rate was 22% (29% for T, and 20% for TC). Median PFS in the whole population was 3.7 months (5.4 months for T, and 3.3 months for TC, p=0.097). The median overall survival in the whole population was 15.4 months: survival was not reached for T, and was 12.3 months for TC patients (p=0.043).
Sunitinib is an active treatment in TETs irrespective of histological subtype, supporting the use of tyrosine kinase inhibitors with anti-angiogenic activity as alternative treatment options in refractory disease.
舒尼替尼是一种有效的口服酪氨酸激酶抑制剂,可抑制血管内皮生长因子受体(VEGFRs)、KIT和血小板衍生生长因子受体(PDGFRs)。在一项单臂II期试验中,舒尼替尼已证明其在难治性胸腺癌(TC)和胸腺瘤(T)中的潜在活性。利用法国RYTHMIC网络前瞻性数据库,我们调查了舒尼替尼在未纳入临床试验的既往治疗过的胸腺上皮肿瘤(TETs)患者中的非适应证疗效。
RYTHMIC数据库始于2012年,前瞻性收集所有诊断为TET且在国家多学科肿瘤委员会讨论其治疗方案的患者的临床、影像、治疗和随访数据。所有接受舒尼替尼治疗的患者均被纳入本分析。
共确定了来自7家机构的28例患者,其中包括20例TC和8例T;32%的患者为女性,中位年龄为50岁。15例患者(54%)接受舒尼替尼作为≥第4线治疗。舒尼替尼的初始日剂量在11例患者中为50mg,16例患者中为37.5mg,1例患者中为25mg。舒尼替尼的不良事件均可控且可耐受;8例患者在中位治疗持续时间2.7个月后因毒性不得不停用舒尼替尼。在总体人群中,疾病控制率为63%(T为86%,TC为55%);总缓解率为22%(T为29%,TC为20%)。总体人群的中位无进展生存期(PFS)为3.7个月(T为5.4个月,TC为3.3个月,p = 0.097)。总体人群的中位总生存期为15.4个月:T患者未达到生存期,TC患者为12.3个月(p = 0.043)。
无论组织学亚型如何,舒尼替尼在TETs中均为一种有效的治疗方法,支持使用具有抗血管生成活性的酪氨酸激酶抑制剂作为难治性疾病的替代治疗选择。