ASCO GU 2018: Subgroup Analysis of Progression-free Survival and Objective Response Rate in the Alliance AO31203 CABOSUN trial - Advanced Renal Cell Carcinoma

San Francisco, CA ( Cabozantinib (Cabo), a small molecule design to target the MET and ALK pathways in addition to VEGFR2 pathway has been shown to be superior to everolimus in the second-line setting (METEOR Trial), and most recently superior to sunitinib (CABOSUN trial) for the treatment of intermediate and poor risk patients with treatment naïve metastatic RCC (mRCC). Dr. George, from Duke Cancer Institute, presents the subgroup analyses of progression-free survival (PFS) and objective response rates (ORR) evaluated from the CABOSUN trial. 

On subgroup PFS and ORR analysis, cabozantinib remained superior to sunitinib among all common clinicopathological factors (age, sex, and ECOG-PS). MET status was associated with a superior ORR (OR 4.71) and PFS (HR 0.32) in those treated with cabozantinib. MET status was associated with a worse PFS in those treated with sunitinib, possibly identifying a prognostic biomarker for patients with intermediate or poor-risk newly diagnosed mRCC. Interestingly, patients with MET-positive tumors fared better in the cabozantinib group with a median progression-free survival of 13.8 months vs. 6.9 months.  This finding possibly identifies MET positivity as a predictive biomarker for patients who are being selected for cabozantinib treatment. cabozantinib remained superior to sunitinib after stratification of patients into intermediate (HR 0.52 [CI 0.32-0.82]) and poor-risk (HR 0.31 [CI 0.11-0.92]) IMDC groups. In regards to patients presenting with bone metastases, cabozantinib was found superior to sunitinib (HR 0.51 [CI0.26-0.99]), which is likely related to its greater bioavailability in the tumor micro-environment. 

In summary, cabozantinib showed improved PFS and ORR compared to sunitinib as an initial targeted therapy for patients with treatment naïve mRCC. The results remained consistent within all the subgroups defined by baseline characteristics. MET positivity has the potential to become a predictive biomarker for patients considering treatment with cabozantinib. 

Presented by:  Daniel J. George, MD, Duke Cancer Institute, Durham NC 

Written by: Andres F. Correa, MD, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA