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Learning How to Manage Immunotherapy or TKI-Related AEs in Advanced RCC

April 16, 2024
By Moshe Ornstein, MD, MA
News
Video

Clinicians are learning how to identify adverse effects relating to either immunotherapy or tyrosine kinase inhibitors for patients with advanced renal cell carcinoma.

Treating advanced renal cell carcinoma (RCC) with immunotherapy has led to a significant improvement in response rates vs a traditional therapy approach.

Moshe Ornstein, MD, discussed determining how to tell if immunotherapy or tyrosine kinase inhibitors (TKIs) are related to certain adverse effects. AEs that are most common with these agents include fatigue, diarrhea, and elevated liver enzymes.

Ornstein, a medical oncologist at the Cleveland Clinic, also spoke about learning whether dose reductions are needed or if suspension of treatment or switching therapies would be more beneficial for an individual patient.

Additionally, if clinicians can better identify the cause of an AE, this will help in creating a personalized treatment plan. Moving forward, Ornstein hopes that additional research will be conducted to better help these personalized treatment plans and to mitigate AEs associated with treatment.

Transcript:

Although the treatment changes for advanced RCC with immunotherapy-based combinations in the frontline [setting] have improved response rates, progression-free survival, and overall survival compared with historical standards, at the end of the day, some of these patients are going to have AEs from treatment. The biggest challenge when it comes to managing the AEs is those AEs can be from either an immunotherapy or from the immunotherapy partner, the TKI. For instance, fatigue, diarrhea, and elevated liver tests can be from immunotherapy or a targeted therapy. Developing a strategy to determine which agent is responsible for that AE is critical in terms of managing the AE, [as well as] knowing which agent a patient can stay on and when and [whether] we can resume the therapy that was on hold while the toxicity was being managed.

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Data from a first-in-disease trial assessing a personalized cancer vaccine in RCC require validation at a larger level, according to David Braun, MD, PhD.
Blood-based markers of note in kidney cancer prognosis include circulating tumor DNA and proteomic markers, according to Michael B. Atkins, MD.
Clinical trials still have a role in improving outcomes with immunotherapy among those with kidney cancer.
Current research initiatives in the kidney cancer field include exploring anti–PD-1, anti–LAG-3, and anti–CTLA-4 combination regimens.
One of the largest obstacles to tackle in the kidney cancer landscape will be translating the research on rare kidney cancer subtypes into clinical trials.
Zanzalitinib exhibited favorable data when evaluated alone or in combination with anti-PD-1 immune checkpoint inhibition in phase 1 RCC trials.
The investigational agent exhibited superior efficacy vs pembrolizumab in patients with lung cancer, suggesting potential efficacy in kidney cancer.
“As a community, if we’re looking to help enroll and advocate for patients with rare [kidney cancers], we need to be aware of what is out there,” said A. Ari Hakimi, MD.
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The developers will present these data at an upcoming medical meeting and plan to begin discussions with regulatory authorities.

Belzutifan Plus Lenvatinib Improves PFS/ORR in Advanced Pretreated RCC

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October 28th 2025
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Belzutifan/lenvatinib also showed a favorable trend towards improvement for overall survival in this advanced renal cell carcinoma population.


Experts share their perspectives on updated clinical trial results, personalized cancer vaccine research, and other notable developments in kidney cancer.

Key Advances Across Kidney Cancer Research and Management at KCRS 2025

Thomas Powles, MBBS, MCRP, MD;David Braun, MD, PhD;Wenxin (Vincent) Xu, MD;Eric Jonasch, MD
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Podcast

Experts share their perspectives on updated clinical trial results, personalized cancer vaccine research, and other notable developments in kidney cancer.


Treatment discontinuation occurred in 9% of patients, of which 1% and 3% were caused by anemia and hypoxia, respectively.

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Tim Cortese
October 6th 2025
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Casdatifan, administered at 100 mg once daily, achieved a confirmed ORR of 35% in patients with pretreated metastatic kidney cancer.


Unveiling Advances in GU Cancers: Insights from Oncology Decoded

Unveiling Advances in GU Cancers: Insights from Oncology Decoded

Manojkumar Bupathi, MD, MS;Benjamin Garmezy, MD;John Burke, MD;Dhaval R. Shah, MBBS
July 3rd 2025
Podcast

Dive into the latest in genitourinary oncology with "Oncology Decoded," featuring discussions on KEYNOTE-564 with RCC.


External validation will be assessed in cohort 2 of the AURORAX-0087A trial to improve recurrence detection for clear cell renal cell carcinoma.

Urine Glycosaminoglycan Scores Show High Sensitivity to Detect ccRCC

Roman Fabbricatore
September 3rd 2025
Article

External validation will be assessed in cohort 2 of the AURORAX-0087A trial to improve recurrence detection for clear cell renal cell carcinoma.


Additional correlative data and further prospective clinical investigations are needed to inform biomarker-directed advanced RCC treatment.

Pembrolizumab Combo Exhibits Sustained Clinical Benefit in Advanced RCC

Roman Fabbricatore
August 22nd 2025
Article

Additional correlative data and further prospective clinical investigations are needed to inform biomarker-directed advanced RCC treatment.

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