ESMO 2016: Cabozantinib Improves Progression-Free Survival in Metastatic Renal Cell Carcinoma
Cabozantinib (Cabometyx, Cometriq) significantly improves progression-free survival and response rate in patients with metastatic renal cell carcinoma compared to sunitinib (Sutent), according to research presented by Choueiri et al at the 2016 European Society for Medical Oncology (ESMO) Congress in Copenhagen (Abstract LBA30_PR).
Cabozantinib targets a class of enzymes called tyrosine kinases but, unlike sunitinib, which targets the vascular endothelial growth factor receptor (VEGFR), cabozantinib additionally inhibits the action of MET and AXL.
“Both MET and AXL seem to be associated with tumor progression, but more importantly, animal models showed that the development of resistance to VEGFR inhibitors like sunitinib can be mediated through AXL and MET,” said principal investigator Toni Choueiri, MD, Director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute.
ALLIANCE A031203
In the phase II ALLIANCE A031203 multicenter trial, 157 patients with untreated clear cell metastatic renal cell carcinoma of intermediate or poor risk were randomized to either oral cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on, 2 weeks off).
Patients treated with cabozantinib showed a 31% reduction in the median rate of progression or death compared to those treated with sunitinib (8.2 vs 5.6 months, P = .012). The objective response rate was also significantly higher in the cabozantinib arm compared to the sunitinib arm (46% vs 18%).
Researchers observed a similar rate of adverse events between the two arms of the study, with the incidence of grade 3 or higher adverse events being 70.5% in the cabozantinib arm and 72.2% in the sunitinib arm. The most common adverse events for both treatments included diarrhea, fatigue, hypertension, palmar-plantar erythrodysesthesia, and hematologic events; 16 patients in each arm terminated their treatment early due to toxicity.
The study did not include good-risk patients, but Dr. Choueiri said there was no biologic or clinical rationale to think that cabozantinib would not be equally effective in that population.
“Cabozantinib is currently approved for second or later lines of therapies, after patients have progressed on a VEGFR tyrosine kinase inhibitor, but these data show that cabozantinib has the potential to become a first-line standard treatment,” Dr. Choueiri concluded.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
