• Thomas Powles, Robert J Motzer, Bernard Escudier, Sumanta Pal, Christian Kollmannsberger, Joanna Pikiel, Howard Gurney, Sun Young Rha, Se Hoon Park, Poul F Geertsen, Marine Gross-Goupil, Enrique Grande, Cristina Suarez, David W Markby, Alan Arroyo, Mark Dean, Toni K Choueiri, and Daniel George.
• Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, Queen Mary, University of London, London, E1 4NS, UK. thomas.powles@bartsandthelondon.nhs.uk.
• Br. J. Cancer. 2018 Sep 1; 119 (6): 663-669.

BackgroundIn the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) versus everolimus in patients with advanced renal cell carcinoma (RCC), after prior antiangiogenic therapy.MethodsOutcomes were evaluated for subgroups defined by prior therapy with sunitinib or pazopanib as the only prior VEGFR inhibitor, or prior anti-PD-1/PD-L1 therapy.ResultsFor the prior sunitinib subgroup (N = 267), median PFS for cabozantinib versus everolimus was 9.1 versus 3.7 months (HR 0.43, 95% CI 0.32-0.59), ORR was 16% versus 3%, and median OS was 21.4 versus 16.5 months (HR 0.66, 95% CI 0.47-0.93). For the prior pazopanib subgroup (N = 171), median PFS for cabozantinib versus everolimus was 7.4 versus 5.1 months (HR 0.67, 95% CI 0.45-0.99), ORR was 19% versus 4%, and median OS was 22.0 versus 17.5 months (HR 0.66, 95% CI 0.42-1.04). For prior anti-PD-1/PD-L1 therapy (N = 32), median PFS was not reached for cabozantinib versus 4.1 months for everolimus (HR 0.22, 95% CI 0.07-0.65), ORR was 22% versus 0%, and median OS was not reached versus 16.3 months (HR 0.56, 95% CI 0.21-1.52).ConclusionsCabozantinib was associated with improved clinical outcomes versus everolimus in patients with advanced RCC, irrespective of prior therapy, including checkpoint inhibitor therapy.

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