A drug whose clinical testing was led by Toni K. Choueiri, MD, of Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC), has become a standard first-line therapy for certain newly diagnosed patients with advanced kidney cancer. Additionally, several combination therapies are being used or tested at DF/BWCC and elsewhere against this aggressive cancer.
The drug cabozantinib (CABOMETYX®) was approved by the U.S. Food and Drug Administration in December for immediate- and poor-risk patients with previously untreated metastatic clear cell renal carcinoma (RCC). Dr. Choueiri, director of the Lank Center for Genitourinary Oncology at DF/BWCC, directed the randomized Phase 2 multicenter study that compared cabozantinib (previously approved as a second line treatment) with sunitinib (Sutent®), which was the standard initial treatment for metastatic kidney cancer for a decade. In the study, subjects who received cabozantinib had a longer time to progression and higher response than those who received sunitinib.
“This drug is very reasonable to use in first-line patients who have bone metastases and in patients who are looking for quick reduction in their metastatic disease burden,” said Dr. Choueiri.
Both sunitinib and cabozantinib inhibit vascular endothelial growth factor (VEGF). Cabozantinib also blocks the MET and AXL proteins, which are both involved in resistance to VEGF inhibitors. This research was reported in the Journal of Clinical Oncology last year.
In other research in intermediate- and poor-risk patients with previously untreated advanced RCC, Choueiri and other CheckMate 214 investigators reported in the New England Journal of Medicine this year that the combination of nivolumab (a PD-1 immune checkpoint inhibitor antibody) plus ipilimumab (which activates the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system) showed significantly higher survival and objective response rates than sunitinib.
In a 2017 review article, also in the New England Journal of Medicine, Dr. Choueiri and Robert J Motzer, MD, of Memorial Sloan Kettering Cancer Center described the ongoing major challenges in addressing RCC as two-fold: 1) identifying blood or tissue biomarkers to predict whether a specific tumor will respond to a specific agent and 2) combining existing treatments with immunotherapy.
Dr. Choueiri continues to be involved in multiple trials for RCC. Learn more about available clinical trials at DF/BWCC.