Cabozantinib plus atezolizumab combination for advanced kidney cancer

In this study, two doses of cabozantinib were tested in combination with atezolizumab for untreated advanced renal cell carcinoma (RCC). Cabozantinib is a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI), while atezolizumab is an immune checkpoint inhibitor.  Two doses of cabozantinib were tested; 40 mg and 60 mg.

The data were fairly comparable between the 40 mg and 60 mg doses, and follow-up continues with the group of patients who received 60 mg of cabozantinib. The time taken for the cancer to start growing again (progression-free survival) was 15 months and 19 months for the 60 mg and 40 mg group respectively. Response rates were around 55 to 60%, which is similar to other TKI plus immunotherapy treatments. Also, there was very low progressive disease, which is very important to patients.

There was no difference in side effects between the two doses of cabozantinib used; however, patient numbers were small at around mid-30 per group.

With so many first-line combination treatments, there needs to be a niche for this combination. Currently, the cabozantinib with nivolumab combination, should represent the new standard of treatment for advance RCC based on the CheckMate 9ER clinical trial data. But there are other combinations, such as nivolumab plus ipilimumab and pembrolizumab plus axitinib. The phase III CONTACT-03 clinical trial should help answer this question. Patients who progress on nivolumab/ipilimumab or axitinib/pembrolizumab can potentially come onto CONTACT-03, where they will be randomised to either cabozantinib at 60 mg or cabozantinib (60 mg) with atezolizumab.

Many doctors use immune checkpoint inhibitors after failure of a prior checkpoint inhibitors, and CONTACT-03 will confirm whether this practice is reasonable and results in clinical benefit.

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