Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI; University of Michigan Rogel Cancer Center, Ann Arbor, MI.
University of Michigan Rogel Cancer Center, Ann Arbor, MI.
Clin Genitourin Cancer. 2020 Aug;18(4):332-339.e2. doi: 10.1016/j.clgc.2019.10.019. Epub 2020 Mar 7.
Cabozantinib is active in advanced prostate cancer with improvement on bone scans in men on phase II trials. This trial evaluated the efficacy and changes in bone lesions in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib.
Eligible patients with mCRPC involving bone underwent biopsy of a bone lesion followed by cabozantinib starting at 60 mg daily and continuing until progression or intolerable toxicity. The primary study endpoint was progression-free survival at 12 weeks. The bone lesion was rebiopsied at 6 weeks. Expression of CMET, phospho-CMET, and VEGFR2 was assayed by immunohistochemistry. Serum was obtained at baseline, and at 3, 6, and 12 weeks and assayed for bone remodeling markers.
A total of 25 patients were enrolled: 22 were evaluable, and 3 were excluded before receiving cabozantinib. At 12 weeks, 17 (77%) of 22 patients had stable disease or better. The median time on treatment was 24 weeks (range, 3-112 weeks). The overall median progression-free survival was 43.7 weeks (95% confidence interval, 23.7-97.0 weeks). Eight (36%) of 22 patients had markedly reduced uptake on bone scan. Patients with significant response on bone scan had higher bone morphogenic protein-2 levels at baseline, stable N-telopeptides levels, increased vascular endothelial growth factor receptor 2 expression, and a trend towards increased phospho-CMET while on cabozantinib compared with patients with stable disease.
Cabozantinib is active in men with mCRPC, inducing significant changes on bone scan in one-third of patients with changes in markers of bone formation and the tumor microenvironment.
卡博替尼在 II 期临床试验中对骨骼扫描有改善作用，可用于治疗晚期前列腺癌。本试验评估了卡博替尼治疗转移性去势抵抗性前列腺癌（mCRPC）患者的疗效和骨病变变化。
有骨转移的 mCRPC 患者，在接受卡博替尼治疗前，先进行骨病变活检，起始剂量为 60mg/天，持续用药直至疾病进展或无法耐受毒性。主要研究终点为 12 周时无进展生存期。6 周时对骨病变进行再次活检。采用免疫组化法检测 CMET、磷酸化 CMET 和 VEGFR2 的表达。在基线、3、6 和 12 周时采集血清，检测骨重塑标志物。
共纳入 25 例患者：22 例可评估，3 例在接受卡博替尼治疗前被排除。12 周时，22 例患者中有 17 例（77%）病情稳定或更好。中位治疗时间为 24 周（范围 3-112 周）。总中位无进展生存期为 43.7 周（95%置信区间，23.7-97.0 周）。22 例患者中有 8 例（36%）骨扫描摄取明显减少。骨扫描有明显缓解的患者，基线时骨形态发生蛋白-2 水平较高，N-端肽水平稳定，血管内皮生长因子受体 2 表达增加，而磷酸化 CMET 则呈上升趋势，与病情稳定的患者相比。
卡博替尼对 mCRPC 患者有效，三分之一的患者骨扫描有明显变化，同时伴有骨形成标志物和肿瘤微环境的变化。
