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als in Oncology with the sponsorship of NCI-CTEP and under a CRADA between Exelixis and NCI-CTEP. Dr. Choueiri is the principal investigator of the study. The primary objective of the study was to evaluate whether progression-free survival with cabozantinib would be improved compared to sunitinib. Secondary endpoints included objective response rate, overall survival and safety. Dr Choueiri: CABOSUN enrolled 157 intermediate or poor risk RCC patients. Patients were stratified by risk group (intermediate vs poor) and presence of bone metastases (yes vs no). 81% of patients were intermediate risk and 19% poor risk; 36% of patients had bone metastases. We presented the results at the 2016 ESMO conference and the data are now published in the Journal of Clinical Oncology.3 CABOSUN met its primary endpoint of significantly improving PFS with cabozantinib as compared with sunitinib: median PFS was “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.” 8.2 months with cabozantinib and 5.6 months with sunitinib. The hazard ratio was 0.66 and the one-sided P value 0.012. Subgroup analyses by stratification factors including risk group and presence of bone metastases consistently favored cabozantinib. The objective response rate was also significantly higher with cabozantinib compared to sunitinib with 46% vs 18% of patients achieving a confirmed objective response. Reductions in target lesion size were seen in 87% on the cabozantinib arm compared to 44% on the 132 Kidney Cancer Journal sunitinib arm. Overall survival results were not mature with a minimum follow-up of 16 months. The median overall survival on cabozantinib was 30.3 months and on sunitinib 21.8 months. The hazard ratio was 0.80 favoring cabozantinib, but the results were not statistically significant. Follow-up is ongoing, and an additional overall survival analysis is planned when the data have further matured. Safety profiles were similar in both treatment arms and the frequency and nature of adverse events was consistent with those previously observed. CABOSUN is the first trial showing a statistically significant and clinically meaningful benefit for a new agent over the standard of care treatment in this setting, sunitinib. These results indicate that cabozantinib may be a potential (Figures 1,2) new treatment option for previously untreated patients with intermediate or poor risk RCC. Dr Figlin: Recent data have suggested that sunitinib may be helpful in high risk resected disease as an adjuvant therapy. Does this mean that cabozantinib might be a treatment choice in this population if they progress following adjuvant therapy? Dr Choueiri: The S-TRAC study was also presented at the 2016 ESMO conference and showed improved disease-free survival in high risk RCC patients who received adjuvant treatment with sunitinib compared with placebo. If sunitinib were adopted as a new treatment option in the adjuvant setting, it is possible that cabozantinib could become a treatment choice after patients progress on adjuvant therapy. In the METEOR trial, cabozantinib showed strong results in the second line setting following first-line sunitinib, and now has demonstrated better outcomes compared to sunitinib in CABOSUN in the first line treatment of intermediate and poor risk RCC patients. Together these data support the use of cabozantinib in the first line after relapse on adjuvant therapy with sunitinib. These results are important when thinking about future trials which could include combinations of cabozan- Table. Summary of METEOR Results Cabozantinib  Everolimus (N=330) (N=328) Median Progression-Free Survival* (mo) 7.4 3.9 95% CI (mo) 6.6, 9.1 3.7, 5.1 PFS Hazard Ratio (95% CI), P value 0.51 (0.41, 0.62), P<0.0001 Median Overall Survival* (mo) 21.4 16.5 95% CI (mo) 18.7, NE 14.7, 18.8 OS Hazard Ratio (95% CI), P value 0.66 (0.53, 0.83), P=0.0003 Objective Response Rate by IRRC (%) 17 3 95% CI (%) 13, 22 2, 6 ORR P value P<0.0001 Pts with Gr3 or4 AE (%) 71 60 Pts with Dose Reductions (%) 62 25 Treatment Discontinuation for AE† (%) 12 11 *As assessed in the entire study population. Study primary endpoint was PFS assessed in first 375 patients enrolled. †Not related to disease progression. IRRC, independent radiological review committee; AE, adverse event. Choueiri TK et al, Lancet Oncol. 2016.


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