ASCO GU 2018: Comparing Cabozantinib Treatment for a Cohort of Patients with Metastatic Clear Cell RCC and Variant Histology RCC: A Retrospective Study

San Francisco, CA ( Dr. Emily Lemke presented results of cabozantinib treatment of patients with metastatic RCC stratified by clear cell and variant histology. Both the randomized METEOR1 and CABOSUN trials2 in clear cell RCC found substantial benefit for patients receiving cabozantinib. To date, there has been no comparative data evaluating the utility of cabozantinib in clear cell RCC and variant histology RCC, thus forming the objective of the current study.

For this study, the authors queried the MD Anderson Cancer Center database to identify patients with metastatic clear cell (n=38) or variant histology RCC (n=30) who received cabozantinib between January 2014 and September 2017. Data collected included baseline characteristics, toxicity, dose reductions, time on cabozantinib, and survival data. Furthermore, a blinded radiologist assessed the radiographic response using RECIST v1.1. Cox regression analysis of time to treatment failure in clear cell RCC and variant histology RCC was performed, adjusting for age, gender, IMDC score, neutrophil to lymphocyte ratio (NLR), prior TKI treatment, and number of metastatic sites. 

Among the 30 patients with variant histology, this included papillary (n=17), chromophobe (n=6), unclassified (n=3), translocation (n=2), sarcomatoid (n=1), and mucinous tubular spindle cell (n=1). There was no difference between clear cell and variant histology groups with regards to male gender, age, NLR, and number of metastatic sites. Patients with clear cell histology had a higher IMDC score compared to variant histology patients (2 vs 1, p=0.024). Time to treatment failure was significantly longer in variant histology RCC compared with clear cell RCC (16.1 vs 7.64 months, HR 0.42, 95%CI 0.22-0.79). Furthermore, this difference persisted in the adjusted Cox regression model (HR 0.36, 95%CI 0.15-0.85).

The authors concluded that in this retrospective comparative analysis of cabozantinib treated variant histology RCC and clear cell RCC patients, cabozantinib was found to have substantial activity in both cohorts of patients, albeit with shorter time to treatment failure for patients with clear cell histology. The IMDC score was important to predict outcome. Both heavily pretreated patients with clear cell and variant histology RCC patients appeared to have substantial benefit.

Presented by: Emily Lemke, DNP, The University of Texas MD Anderson Cancer Center, Houston, TX

Co-Authors: Amishi Yogesh Shah, Pavlos Msaouel, Mehmet Asim Bilen, Eric Jonasch, Aradhana M. Venkatesan, Anuradha Chandramohan, Cihan Duran, Nizar M. Tannir, Matthew T. Campbell

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, @zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA


1. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015;373(19):1814-1823.

2. Choueiri TK, Halabi S, Sanford BL, 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 2017;35(6):591-597.