Activity of cabozantinib (XL184) in metastatic melanoma: Results from a phase II randomized discontinuation trial (RDT).

8531 Background: MET and VEGF signaling are implicated in angiogenesis, invasion, and metastasis. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types. Here we report on the metastatic melanoma cohort, including the ocular subtype. Methods: Eligible patients (pts) were required to have progressive measurable disease per RECIST. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Primary endpoint in the randomized phase was progression free survival (PFS). Results: Enrollment to this cohort is complete (n = 77); all pts are unblinded. Baseline characteristics: median age 66 years; melanoma subtype: cutaneous/mucosal 70% and ocular 30%; known BRAF mutation 32%; LDH ≥ 1.1 x upper limit normal 35%; bone metastases 19%; median prior lin...

8531背景：MET和血管内皮生长因子（VEGF）信号传导与血管生成、侵袭和转移有关。卡博替尼（cabo）是一种口服的MET和VEGFR2强效抑制剂。一项随机停药试验（RDT）评估了其在9种肿瘤类型中的活性和安全性。在此我们报告转移性黑色素瘤队列的情况，包括眼部亚型。 方法：符合条件的患者（pts）需根据实体瘤疗效评价标准（RECIST）有进展性可测量疾病。患者在12周导入期接受每日1次100mg的卡博替尼治疗。每6周评估一次肿瘤反应（改良实体瘤疗效评价标准，mRECIST）。第12周后的治疗基于反应情况：部分缓解（PR）的患者继续接受卡博替尼开放标签治疗，疾病稳定（SD）的患者随机接受卡博替尼或安慰剂治疗，疾病进展（PD）的患者停止治疗。随机阶段的主要终点是无进展生存期（PFS）。 结果：该队列的招募已完成（n = 77）；所有患者均已揭盲。基线特征：中位年龄66岁；黑色素瘤亚型：皮肤/黏膜型70%，眼部30%；已知BRAF突变32%；乳酸脱氢酶（LDH）≥正常上限的1.1倍占35%；骨转移19%；既往治疗线数中位数……