Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Anatomical Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2020 Mar 1;26(5):990-999. doi: 10.1158/1078-0432.CCR-19-2389. Epub 2020 Jan 15.
Cabozantinib, an oral inhibitor of c-MET/VEGFR2 signaling, improved progression-free survival (mPFS) but not overall survival (OS) in metastatic castrate-resistant prostate cancer. We evaluated cabozantinib plus androgen deprivation therapy (ADT) in hormone-naïve metastatic prostate cancer (HNMPCa).
Patients received ADT plus cabozantinib starting at 60 mg daily. The primary endpoint was castrate-resistant PFS by radiographic criteria, clinical progression, or receipt of additional therapy. Secondary endpoints included OS, safety, radiographic responses, and biomarker modulation.
Sixty-two patients received treatment. With a median follow-up of 31.2 months, the mPFS was 16.1 months (95% CI, 14.6-22.7 months), and mOS was not reached. Reductions in PSA ≥ 90%, bone-specific alkaline phosphatase ≥ 50%, and urine N-telopeptides ≥ 50% occurred in 83%, 87%, and 86% of evaluable patients, respectively. Responses in bone scan and measurable disease were observed in 81% of and 90% of evaluable patients, respectively. Most common grade 3 adverse events were hypertension (19%), diarrhea (6%), and thromboembolic events (6%), and dose reductions occurred in 85% of patients. Analysis of baseline cytokine and angiogenic factors (CAFs) revealed that higher plasma concentrations of Lumican, CXCL5, CD25, and CD30 were associated with shorter PFS as was high tumor expression of pFGFR1.
Cabozantinib plus ADT has promising clinical activity in HNMPCa. CAF profiles and tissue markers suggest candidate prognostic and predictive markers of cabozantinib benefit and provide insights for rational therapy combinations.
卡博替尼是一种口服的 c-MET/VEGFR2 信号抑制剂，可改善转移性去势抵抗性前列腺癌（mCRPC）患者的无进展生存期（mPFS），但不改善总生存期（OS）。我们评估了卡博替尼联合雄激素剥夺治疗（ADT）在激素初治转移性前列腺癌（HNMPCa）中的疗效。
患者接受 ADT 联合卡博替尼治疗，起始剂量为 60mg/天。主要终点是根据影像学标准、临床进展或接受其他治疗的情况评估的去势抵抗性 PFS。次要终点包括 OS、安全性、影像学反应和生物标志物的变化。
62 例患者接受了治疗。中位随访 31.2 个月时，mPFS 为 16.1 个月（95%CI，14.6-22.7 个月），mOS 尚未达到。可评估患者中分别有 83%、87%和 86%的患者 PSA 降低≥90%、碱性磷酸酶骨特异性≥50%和尿 N-末端肽≥50%，骨扫描和可测量疾病的缓解率分别为 81%和 90%。最常见的 3 级不良事件是高血压（19%）、腹泻（6%）和血栓栓塞事件（6%），85%的患者需要减少剂量。对基线细胞因子和血管生成因子（CAFs）的分析表明，血浆中 Lumican、CXCL5、CD25 和 CD30 浓度较高与 PFS 较短相关，肿瘤中 pFGFR1 的高表达也与 PFS 较短相关。
卡博替尼联合 ADT 在 HNMPCa 中具有良好的临床活性。CAF 谱和组织标志物提示卡博替尼获益的候选预后和预测标志物，并为合理的治疗联合提供了见解。
