Tyrosine kinase inhibitors have been successfully developed in combination with immune checkpoint inhibitors to treat advanced renal cell carcinoma (RCC), further advancing treatment. While safety profiles are generally manageable with combination regimens, overlapping adverse events (AEs) and immune-related AEs can make treatment more complex.
The CheckMate 9ER study evaluated the tyrosine kinase inhibitor cabozantinib in combination with the anti-programmed cell death protein-1 antibody nivolumab in patients with previously untreated advanced RCC. Cabozantinib + nivolumab demonstrated superiority over sunitinib for progression-free survival, overall survival, and objective response rate. These outcomes supported the approval of cabozantinib + nivolumab as a first-line therapy for advanced RCC. The safety profile was manageable with prophylaxis, supportive care, dose holds and reductions for cabozantinib, and dose holds and immunosuppressive therapy for nivolumab. This review discusses the safety results of CheckMate 9ER and provides guidance on managing some of the more clinically relevant AEs with a focus on overlapping AEs, including diarrhea, elevated amylase/lipase, hepatotoxicity, dermatologic reactions, fatigue, endocrine disorders, and nephrotoxicity. We discuss AE management strategies (prophylaxis, supportive care, dose modification, and immunosuppressive therapy), and provide recommendations for identifying the causative agent of overlapping AEs and for consulting specialists about organ-specific immune-related AEs. Optimizing AE management can maintain tolerability and should be a priority with cabozantinib + nivolumab treatment.
Cancer treatment reviews. 2021 Dec 24 [Epub ahead of print]
Bradley McGregor, Amir Mortazavi, Lisa Cordes, Cristina Salabao, Susan Vandlik, Andrea B Apolo
Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, and the Comprehensive Cancer Center, Columbus, OH, USA., National Cancer Institute and the Office of Clinical Research at the National Institutes of Health, Bethesda, MD, USA., The Ohio State University Wexner Medical Center and the Comprehensive Cancer Center, Columbus, OH, USA., Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35033866