I. Alex Bowman, MD is a Genitourinary Medical Oncologist at the Banner Gateway Medical Center in Gilbert, AZ.

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.

Videos

Dr Bowman discusses immune-related and TKI-specific toxicities when combining immunotherapy and TKIs in non–clear cell RCC.

Dr Bowman on the Role of Kidney Cancer Awareness in Earlier Detection and Improved Patient Outcomes

"Raising awareness for kidney cancer is important for supporting patients and their families as they navigate the challenges of this diagnosis."

I. Alex Bowman, MD, the co-director of the Genitourinary Oncology Program at Banner MD Anderson Cancer Center and is an adjunct assistant professor at The University of Texas MD Anderson Cancer Center, highlights the importance of Kidney Cancer Awareness initiatives in driving earlier disease detection, centering patient education, and spotlighting key treatment advancements in renal cell carcinoma (RCC).

Unlike other malignancies with routine screening protocols, kidney cancer is most often diagnosed through imaging obtained for unrelated conditions, Bowman explained. In some cases, a kidney cancer diagnosis follows the presentation of nonspecific symptoms such as hematuria, flank pain, or fatigue. Although these symptoms are common across many benign conditions, they may signal the presence of an underlying malignancy and warrant further evaluation, particularly in high-risk patient populations, Bowman emphasizes. He stresses that awareness efforts should focus on educating both patients and providers about these early warning signs to support more timely diagnosis.

For individuals with known hereditary cancer syndromes—such as von Hippel-Lindau disease, tuberous sclerosis complex, and Birt-Hogg-Dubé syndrome—proactive screening is essential, Bowman adds. Targeted awareness campaigns may encourage these individuals to engage in earlier discussions with their providers regarding genetic risk and surveillance strategies, he says.

Beyond symptom recognition, Bowman emphasizes the importance of public awareness in supporting ongoing RCC research. The incorporation of immunotherapy and targeted agents into the RCC treatment arsenal has transformed treatment approaches, but continued progress relies on robust support for clinical trials and translational research, he notes.

Bowman concludes by stating that Kidney Cancer Awareness efforts provide much-needed visibility for patients and families navigating a challenging diagnosis. By promoting education, encouraging early intervention, and driving research investment, Kidney Cancer Awareness Month plays a central role in improving outcomes across the spectrum of this disease.

Alex Bowman, MD, discusses the need for early symptom recognition, genetic risk evaluation, and research support to improve RCC detection and outcomes.

I. Alex Bowman, MD, assistant professor, Division of Hematology/Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the rationale for an exploratory, early phase I clinical trial (NCT04006522) of radio-labeled 

Zr-atezolizumab (Tecentriq) PET/CT scans in renal cell carcinoma (RCC). 

In several cancers, it has been found that the amount of PD-L1 expression in the tumor and the tumor microenvironment correlates with response to immunotherapy; however, this has not been the case in kidney cancer, says Bowman.

Several major immunotherapy trials have examined the question of why this is. It is hypothesized that PD-L1 expression will have to be present in the tumor or the surrounding tissue in order for patients to respond to immunotherapy, so either the PD-L1 is not adequately being detected or this expression might be variable within the tumors or different metastatic sites, explains Bowman.

As such, this exploratory clinical trial aims to provide a noninvasive way to detect PD-L1 expression in 2 cohorts: patients with localized RCC who will undergo 

Zr-atezolizumab PET/CT prior to nephrectomy and patients with metastatic RCC who will undergo

Zr-atezolizumab PET/CT prior to treatment with an immune checkpoint inhibitor.  

Co-primary endpoints of the trial will be an exploratory analysis correlating 

Zr-atezolizumab uptake with PD-L1 immunohistochemical analyses in patients with localized advanced disease, as well as an examination of whether 

Zr-atezolizumab uptake across metastatic sites of kidney cancer correlates with knwon radiographically evident metastatic sites of disease, PD-L1 expression, and response to checkpoint inhibitor therapy.

I. Alex Bowman, MD, discusses the rationale for an exploratory clinical trial of radio-labeled 89Zr-atezolizumab PET/CT scans in renal cell carcinoma.
 

I. Alex Bowman, MD

Articles

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

Dr Bowman on the Role of Kidney Cancer Awareness in Earlier Detection and Improved Patient Outcomes

Dr. Bowman on Rationale for Radio-Labeled Atezolizumab PET/CT Scans in RCC