Spotlight on cabozantinib for previously untreated advanced renal cell carcinoma: evidence to date

Background: In recent years, several new agents have emerged as first-line treatments for metastatic renal cell carcinoma (mRCC), including cabozantinib. This systematic review aims to summarize the current evidence regarding the use of cabozantinib as a first-line therapy in mRCC, evaluating outcomes across all reported clinical endpoints.
Methods: This review was conducted in accordance with PRISMA guidelines. A systematic search of PubMed and major oncology conference databases was performed from inception to June 25, 2018. Search terms included: “cabozantinib” OR “cabozantinib-s-malate” OR “XL184” AND “renal cell carcinoma” OR “kidney cancer” OR “clear cell renal carcinoma” OR “renal cancer” AND “first-line” OR “untreated” OR “treatment-naïve” OR “primary treatment.” All original clinical studies assessing cabozantinib alone or in combination with other systemic therapies in previously untreated mRCC patients were considered.
Results: Of 75 initial titles and abstracts, seven studies met inclusion criteria. These included the primary report of the randomized CABOSUN trial, four subsequent publications with updates, subgroup, or secondary analyses from the same cohort, and two network meta-analyses. An additional search identified six ongoing clinical trials evaluating cabozantinib in this setting.
Conclusion: Current evidence supports cabozantinib as a potential first-line treatment option for mRCC patients with intermediate or poor risk per the International Metastatic Renal Cell Carcinoma Database Consortium criteria. It demonstrates a clear benefit in progression-free survival, despite notable Grade 3–4 toxicities, a modest objective response rate, and no overall survival benefit. However, considering the demonstrated survival advantage of immunotherapy-based combinations in this population and the proven efficacy of cabozantinib in the second-line setting, its role may be best positioned as a subsequent therapy following progression on frontline treatment.