Purpose Cabozantinib, an inhibitor of tyrosine kinases including MET, vascular endothelial growth factor receptors, and AXL, increased progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients with advanced renal cell carcinoma (RCC) after previous vascular endothelial growth factor receptor-targeted therapy in the phase III METEOR trial. Because bone metastases are associated with increased morbidity in patients with RCC, bone-related outcomes were analyzed in METEOR. Patients and Methods Six hundred fifty-eight patients were randomly assigned 1:1 to receive 60 mg cabozantinib or 10 mg everolimus. Prespecified subgroup analyses of PFS, OS, and ORR were conducted in patients grouped by baseline bone metastases status per independent radiology committee (IRC). Additional end points included bone scan response per IRC, skeletal-related events, and changes in bone biomarkers. Results For patients with bone metastases at baseline (cabozantinib [n = 77]; everolimus [n = 65]), median PFS was 7.4 months for cabozantinib versus 2.7 months for everolimus (hazard ratio, 0.33 [95% CI, 0.21 to 0.51]). Median OS was also longer with cabozantinib (20.1 months v 12.1 months; hazard ratio, 0.54 [95% CI, 0.34 to 0.84]), and ORR per IRC was higher (17% v 0%). The rate of skeletal-related events was 23% with cabozantinib and 29% with everolimus, and bone scan response per IRC was 20% versus 10%, respectively. PFS, OS, and ORR were also improved with cabozantinib in patients without bone metastases. Changes in bone biomarkers were greater with cabozantinib than with everolimus. The overall safety profiles of cabozantinib and everolimus in patients with bone metastases were consistent with those observed in patients without bone metastases. Conclusion Cabozantinib treatment was associated with improved PFS, OS, and ORR when compared with everolimus treatment in patients with advanced RCC and bone metastases and represents a good treatment option for these patients.

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卡博替尼，晚期肾细胞癌和骨转移患者的新护理标准？METEOR 试验的亚组分析

目的卡博替尼是一种酪氨酸激酶抑制剂，包括 MET、血管内皮生长因子受体和 AXL，可提高晚期肾细胞癌患者的无进展生存期 (PFS)、总生存期 (OS) 和客观缓解率 (ORR)。 RCC) 在 III 期 METEOR 试验中先前的血管内皮生长因子受体靶向治疗之后。由于骨转移与 RCC 患者的发病率增加有关，因此在 METEOR 中分析了骨相关结果。患者和方法 658 名患者以 1:1 的比例随机分配接受 60 mg cabozantinib 或 10 mg 依维莫司。根据独立放射学委员会 (IRC)，在按基线骨转移状态分组的患者中进行 PFS、OS 和 ORR 的预先指定亚组分析。其他终点包括每个 IRC 的骨扫描反应、骨骼相关事件和骨生物标志物的变化。结果 对于基线时发生骨转移的患者（卡博替尼 [n = 77]；依维莫司 [n = 65]），卡博替尼的中位 PFS 为 7.4 个月，而依维莫司的中位 PFS 为 2.7 个月（风险比，0.33 [95% CI，0.21 至 0.51] ）。卡博替尼的中位 OS 也更长（20.1 个月对 12.1 个月；风险比，0.54 [95% CI，0.34 到 0.84]），并且每个 IRC 的 ORR 更高（17% 对 0%）。卡博替尼的骨骼相关事件发生率为 23%，依维莫司为 29%，每个 IRC 的骨扫描反应分别为 20% 和 10%。在没有骨转移的患者中，卡博替尼也改善了 PFS、OS 和 ORR。与依维莫司相比，卡博替尼的骨生物标志物变化更大。卡博替尼和依维莫司在骨转移患者中的总体安全性与在无骨转移患者中观察到的一致。结论 与依维莫司治疗相比，卡博替尼治疗与晚期 RCC 和骨转移患者的 PFS、OS 和 ORR 改善相关，是这些患者的良好治疗选择。