Cabozantinib Sunitinib N Median PFS (95% CI), mo HR (95% CI)* tinib and immune checkpoint inhibitors such as nivolumab, as both agents have shown significant singleagent activity in the treatment of RCC. Dr Figlin: Since cabozantinib targets many pathways, are there any updates on biomarkers that speak to how this agent works and benefits patients? Dr Choueiri: Caboantinib’s targets include MET, AXL and VEGFRs. The superiority of cabozantinib over sunitinib observed in CABOSUN may reflect this differentiated target profile of cabozantinib. Further investigation of biomarkers is currently ongoing and may help to clearly define the roles of these targets in the clinical activity of cabozantinib. However, the role of MET tumor expression was investigated in the METEOR trial and was not found to be predictive of the clinical activity of cabozantinib over everolimus. Additionally, cabozantinib has been shown to have immunomodulatory effects in the tumor microenvironment, supporting the ongoing evaluation Change From Baseline (%) Change From Baseline (%) of the combination of cabozantinib with immune checkpoint inhibition. References 1. Choueiri, TK, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015. 373(19):1814-23. 2. Choueiri, TK, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-27. 3. Choueiri, TK, et al. Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. J Clin Oncol. DOI: 10.1200/JCO.2016.70.7398. Published online before print November 14, 2016. KCJ Kidney Cancer Journal 133 1.0 0.8 0.6 0.4 0.2 0.0 Progresion-Free Survival (probability) 0 6 12 18 24 Time Since Randomization (months) No. at Risk Cabozantinib 79 49 22 9 1 Sunitinib 78 32 15 3 0 Arm Cabozantinib 79 8.2 (6.2, 8.8) 78 5.6 (3.4, 8.1) 0.66 (0.46-0.95) Sunitinib P-value (one-sided) = 0.012 Figure 1. Kaplan-Meier Plot of Progression-Free Survival in the CABOSUN Trial. Best target lesion change from baseline with cabozantinib (left) and sunitinib (right). Three patients in the cabozantinib group and 16 patients in the sunitinib group were not evaluable because they had no postbaseline imaging assessments. 100 50 0 -50 -100 Best Target Lesion Not evaluated: n=3 Cabozantinib 100 50 0 -50 -100 Best Target Lesion Not evaluated: n=16 Sunitinib Figure 2. Best Target Lesion Change from Baseline in CABOSUN Best target lesion change from baseline with cabozantinib (left) and sunitinib (right). Three patients in the cabozantinib group and 16 patients in the sunitinib group were not evaluable because they had no postbaseline imaging assessments. Choueiri TK et al. J Clin Oncol 2016
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