Bernard Escudier, Institut Gustave Roussy, Villejuif; Stephane Oudard, Hôpital Européen Georges Pompidou, Paris; Frederic Rolland, Centre René Gauducheau Centre de Lutte Contre Le Cancer Nantes, Saint-Herblain, France; Thomas Powles, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Robert J. Motzer, Memorial Sloan Kettering Cancer Center, New York, NY; Thomas Olencki, Ohio State University, Columbus, OH; Osvaldo Arén Frontera, Centro Internacional de Estudios Clinicos, Santiago, Chile; Piotr Tomczak, Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego, Poznań, Poland; Daniel Castellano, Hospital Universitario 12 de Octubre, Madrid, Spain; Leonard J Appleman, University of Pittsburgh Medical Center, Pittsburgh, PA; Harry Drabkin, Medical University of South Carolina, Charleston, SC; Daniel Vaena, University of Iowa Hospitals and Clinics, Iowa City, IA; Steven Milwee, Jillian Youkstetter, and Julie C. Lougheed, Exelixis, Inc., San Francisco, CA; Sergio Bracarda, Ospedale San Donato, Istituto Toscano Tumori (ITT), Arezzo, Italy; and Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA.
J Clin Oncol. 2018 Mar 10;36(8):765-772. doi: 10.1200/JCO.2017.74.7352. Epub 2018 Jan 8.
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.
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，在 III 期 METEOR 试验中，在先前接受血管内皮生长因子受体靶向治疗的晚期肾细胞癌（RCC）患者中，卡博替尼增加了无进展生存期（PFS）、总生存期（OS）和客观缓解率（ORR）。由于骨转移与 RCC 患者的发病率增加有关，因此在 METEOR 中分析了与骨相关的结局。
658 例患者按 1:1 随机分配接受 60mg 卡博替尼或 10mg 依维莫司。根据独立放射学委员会（IRC）的基线骨转移状态，对 PFS、OS 和 ORR 进行了预设亚组分析。其他终点包括 IRC 评估的骨扫描反应、骨骼相关事件和骨生物标志物的变化。
对于基线有骨转移的患者（卡博替尼组 [n=77]；依维莫司组 [n=65]），卡博替尼组的中位 PFS 为 7.4 个月，依维莫司组为 2.7 个月（风险比，0.33 [95%CI，0.21 至 0.51]）。卡博替尼组的中位 OS 也更长（20.1 个月比 12.1 个月；风险比，0.54 [95%CI，0.34 至 0.84]），IRC 评估的 ORR 更高（17%比 0%）。卡博替尼组的骨骼相关事件发生率为 23%，依维莫司组为 29%，IRC 评估的骨扫描反应率分别为 20%和 10%。在无骨转移的患者中，卡博替尼也改善了 PFS、OS 和 ORR。与依维莫司相比，卡博替尼治疗后骨生物标志物的变化更大。在有或无骨转移的患者中，卡博替尼和依维莫司的总体安全性特征一致。
与依维莫司相比，卡博替尼治疗晚期 RCC 伴骨转移患者可改善 PFS、OS 和 ORR，是这些患者的一种较好的治疗选择。
