Cabozantinib, a New Standard of Care for Patients With Advanced Renal Cell Carcinoma and Bone Metastases? Subgroup Analysis of the METEOR Trial

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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 Jan 08 [Epub ahead of print]

Bernard Escudier, Thomas Powles, Robert J Motzer, Thomas Olencki, Osvaldo Arén Frontera, Stephane Oudard, Frederic Rolland, Piotr Tomczak, Daniel Castellano, Leonard J Appleman, Harry Drabkin, Daniel Vaena, Steven Milwee, Jillian Youkstetter, Julie C Lougheed, Sergio Bracarda, Toni K Choueiri

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.