Effective Treatment Strategies for Renal Medullary Carcinoma

Renal medullary carcinoma (RMC) requires a specialized treatment approach because it is biologically distinct from more common kidney cancers like clear cell renal cell carcinoma (ccRCC). Pavlos Msaouel, MD, PhD, associate professor at The University of Texas MD Anderson Cancer Center in Houston, explains that RMC arises under conditions of extreme hypoxia and typically involves the loss of SMARCB1, which protects the tumor from certain standard therapies.

Clinical trials show that standard immune checkpoint therapies, including single-agent pembrolizumab (Keytruda) or the combination of nivolumab (Opdivo) and ipilimumab (Yervoy), are ineffective and may even cause hyperprogression in RMC cells. Consequently, these should be avoided outside of clinical trials. Furthermore, standard VEGF-targeted therapies such as cabozantinib (Cabometyx), bevacizumab, and lenvatinib do not work against RMC because the disease does not rely on blood vessels in the same manner as ccRCC.

While RMC is resistant to many common treatments, specific protocols have shown efficacy. Platinum-based chemotherapy remains a core treatment for RMC, and EGFR-targeting agents have been established as a viable approach by Dr Msaouel's team. Additionally, antibody-drug conjugates represent a promising therapy for RMC patients.

Dr Msaouel notes that RMC is also distinct from urothelial carcinomas. Unlike bladder cancer, RMC is not sensitive to the methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin regimen and does not typically express Nectin-4 or HER2, meaning targeted therapies for those molecules are ineffective. Research continues to focus on breaking barriers to successfully harness the immune system specifically for RMC.