Dr Bowman on the Safety of TKI and Immunotherapy Combinations in Non–Clear Cell RCC

"The immune system is a very individual and powerful entity, and anybody can have any kind of [adverse] effect [AEs] with these immunotherapies; fortunately, the risk of severe AEs is relatively low."

I. Alex Bowman, MD, a medical oncologist and genitourinary malignancies specialist at Banner Health, discusses safety considerations surrounding the use of TKI and immune-oncology (IO) combinations in the first-line treatment of patients with advanced non–clear cell renal cell carcinoma (RCC).

Although the IO/TKI combination strategy has demonstrated efficacy in metastatic RCC, understanding the distinct toxicity profiles of each agent class is essential when applying this regimen in clinical practice, Bowman explained. Immune checkpoint inhibitors, which are a core component of these regimens, have now been integrated into routine oncologic care for over a decade. These agents function by stimulating the immune system to mount a response against tumor cells; however, they can also lead to immune-related adverse effects (irAEs), he said.

The most frequently encountered irAEs mimic autoimmune processes, Bowman continued. Immune-mediated colitis, for instance, may present with diarrhea secondary to gastrointestinal tract inflammation. Musculoskeletal inflammation, manifesting as myositis or arthritis, is also observed. Although irAEs may affect a wide range of organ systems, the incidence of severe toxicities remains relatively low, Bowman emphasized. Importantly, early detection and appropriate immunosuppressive management typically result in resolution of these AEs without long-term sequelae.

Conversely, TKIs are associated with a different AE spectrum. These agents target angiogenesis and tumor proliferation pathways and are more commonly associated with hypertension, hand-foot syndrome, and gastrointestinal toxicity, Bowman noted. When TKIs and IO agents are used in combination, oncologists must distinguish overlapping toxicities and evaluate each AE independently, he said.

The safety of IO/TKI regimens in non–clear cell RCC is particularly relevant, given the historical paucity of effective treatment options in this population, Bowman underscored. Individualized toxicity monitoring and patient selection are important implementing these regimens, he said, highlighting the need for a multidisciplinary care approach, particularly in community practices, to ensure that irAEs are identified early and managed appropriately.