Cabozantinib, Nivolumab With or Without Ipilimumab Improves ORR for GU Cancers

A recent phase 1, dose-escalation study demonstrated the safety and efficacy of cabozantinib plus nivolumab alone (cabo/nivo) or in combination with ipilimumab (cabo/nivo/ipi) for several genitourinary diseases, including metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).

Andrea Apolo, MD, and colleagues released a final data analysis of the study and 7 expansion cohorts, including overall response rate (ORR), progression-free survival, and overall survival results.

The multicenter, investigator-initiated trial utilized 3 expansion cohorts examining the effect of cabo/nivo for mUC, mRCC, and adenocarcinoma of the bladder or urachal.

Triplet expansion cohorts examined cabo/nivo/ipi for mUC, mRCC, penile cancer, and squamous cell carcinoma of the bladder and other rare genitourinary tumors.

Of the 120 patients enrolled, 108 were evaluable. Cabo/nivo was administered to 59 patients, while 49 patients received cabo/nivo/ipi. The ORR was 38%, the complete response rate was 11%, and the median duration of response was 20 months. The median follow-up was 49.2 months.

The ORR results by disease state were 42.4% for mUC, 62.5% for mRCC (n=16), 85.7% for squamous cell carcinoma of the bladder (n=7), 44.4% for penile cancer (n=9), and 50.0% for renal medullary carcinoma (n=2). Grade ≥3 treatment-related adverse events occurred in 84% of cabo/nivo patients and 80% of cabo/nivo/ipi patients.

The combination treatments of cabo/nivo and cabo/nivo/ipi provide beneficial clinical activity and safety in the treatment of multiple GU malignancies.