Dual therapy with a tyrosine kinase inhibitor (TKI) and either a programmed death protein/ligand 1 (PD-1/PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor has proven efficacy as treatment for previously-untreated advanced renal cell carcinoma (RCC). The combination of the multi-targeted TKI cabozantinib (Cabometyx®) and the anti-PD-1 monoclonal antibody nivolumab (Opdivo®) is approved as first line treatment for RCC in the EU, USA and multiple other countries. In the CheckMate 9ER trial, combination therapy with cabozantinib and nivolumab was superior to sunitinib monotherapy as first line treatment for advanced RCC, demonstrating significantly longer progression-free survival and, importantly, improved overall survival. Patients receiving the combination were also more likely to respond than those treated with sunitinib monotherapy. In addition, health-related quality of life was significantly better with cabozantinib plus nivolumab at nearly all time points during the study. The tolerability profile of the combination was consistent with that seen in previous studies evaluating the two drugs as monotherapy, although more patients who received the combination had serious adverse events than those treated with sunitinib monotherapy. In summary, cabozantinib plus nivolumab is a recommended option for first-line treatment of previously-untreated advanced RCC.
Advanced renal cell carcinoma (RCC) is a difficult-to-treat disease with a poor prognosis. The introduction of targeted therapy and, subsequently, treatments that boost or restore the patient’s natural immune response to cancer (immunotherapy), however, has led to improved outcomes. In particular, combination treatment with a targeted therapy drug and an immunotherapeutic agent has been shown to significantly improve overall survival compared to targeted therapy alone. Dual therapy with the tyrosine kinase inhibitor cabozantinib (Cabometyx®) and the PD-1 inhibitor nivolumab (Opdivo®) is approved for the first line treatment of advanced RCC in multiple countries. In the CheckMate 9ER trial, cabozantinib plus nivolumab significantly improved progression-free and overall survival in patients with previously untreated RCC compared to monotherapy with an older drug (sunitinib). The combination was also associated with better quality of life than sunitinib monotherapy. Although the tolerability profile of the combination was consistent with that seen in previous studies evaluating the two drugs as monotherapy, more patients who received the combination had serious adverse events than those treated with sunitinib. In summary, cabozantinib plus nivolumab is a recommended option for first-line treatment of previously-untreated advanced RCC.
Targeted oncology. 2022 Feb 17 [Epub ahead of print]
Anthony Markham
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. .