What Patients With Kidney Cancer Need to Know From ASCO GU

There were a number of notable developments for patients with kidney cancer at the symposium: © SciePro - stock.adobe.com

At the 2025 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, there were a number of notable developments for patients with kidney cancer, Dr. Emre Yekedüz explained in an interview with CURE.

Yekedüz is a medical oncologist and research fellow in medicine at Dana-Farber Cancer Institute in Boston.

CURE: What were the most important takeaways from the symposium regarding kidney cancer treatment?

Yekedüz: I can name the three most important key takeaways for our patients from the ASCO GU 2025 symposium. The first promising advancement is the combination regimen of Lenvima (lenvatinib), a tyrosine kinase inhibitor used in kidney cancer patients, and Welireg (belzutifan), a HIF-2α inhibitor also used in kidney cancer. This combination shows promise in second-line treatment and beyond for patients with metastatic clear cell RCC.

The second advancement is KIM-1, the kidney injury molecule-1, a promising biomarker for evaluating prognosis and predicting survival in metastatic clear cell RCC patients receiving Opdivo (nivolumab) plus Yervoy (ipilimumab). These are the immune checkpoint inhibitors used in our kidney cancer patients.

The third is a novel HIF-2α inhibitor, a target for kidney cancer patients. Casdatifan is currently under development. An early phase 1 trial, presented by Dr. Toni Choueiri, showed a 30% objective response rate as a single agent in second-line treatment and beyond for patients with metastatic clear cell renal cell carcinoma (RCC). We are now awaiting other combinations in phase 3 trials. This is a novel and promising agent for our kidney cancer patients.

Were there any significant advancements in targeted therapies or immunotherapy for kidney cancer presented at the symposium?

The first promising development is the Lenvima plus Welireg combination. Lenvima is a tyrosine kinase inhibitor, and Welireg is a HIF-2α inhibitor. This combination has a 47% objective response rate in a phase 2 trial, suggesting it's a promising treatment for previously treated metastatic clear cell RCC patients. Based on these results, we are awaiting the LITESPARK-011 trial. This phase 3 trial compares the Lenvima plus Welireg combination versus Cabometyx (cabozantinib), another tyrosine kinase inhibitor, in previously treated metastatic clear cell RCC patients. We are very excited about this combination for our patients.

The second advancement is Lenvima, the tyrosine kinase inhibitor, plus Tevimbra (tislelizumab), an immune checkpoint inhibitor. This combination is being explored in fumarate hydratase-deficient RCC, a very rare subtype of non-clear cell RCC. We categorize RCC patients into clear cell and non-clear cell, and the non-clear cell group includes very rare subtypes. Fumarate hydratase-deficient RCC accounts for approximately 1% to 2% of all cases. A phase 2 trial evaluating Lenvima plus Tevimbra demonstrated an extremely high objective response rate, almost 90%, with 20% of patients achieving a complete response, meaning no primary disease progression. All patients achieved disease control, and this combination may be a promising first-line standard of care treatment option for patients with fumarate hydratase-deficient RCC.

ctDNA and biomarkers in this treatment field are gaining attention and have been for a while now. What role do these play in kidney cancer treatment, and can they help guide personalized treatment?

ctDNA is a really useful biomarker in all types of cancer. We can use ctDNA for cancer screening, early cancer detection, from diagnosis to the metastatic stage; we can use it at every step during the cancer course. Numerous trials and studies are ongoing. However, we still need time to use it in our clinical practice for kidney cancer patients. But we can ask some questions about how we can use ctDNA in our patients. The first question is: Is there any role for ctDNA in small renal masses, and can we use it to select patients for surgery, other local ablative therapies, or observation? The second question is: Can we use ctDNA to select patients after surgery to give them adjuvant Keytruda (pembrolizumab)? Adjuvant Keytruda is a standard of care in the adjuvant setting to prevent disease recurrence. So, can we use ctDNA to select patients for adjuvant Keytruda or observation? And the third question is: Can we use ctDNA in the metastatic setting for prognosis or predicting treatment response?

In light of these questions, there was a trial presented at ASCO GU 2025, the CALYPSO trial. This phase 2 trial evaluated the efficacy of Imfinzi (durvalumab), an immune checkpoint inhibitor, plus savolitinib, a c-MET-targeted tyrosine kinase inhibitor, in patients with papillary cell RCC. The exploratory analysis of this trial showed that baseline ctDNA and ctDNA clearance were prognostic, and high ctDNA levels were associated with worse survival outcomes. We need further studies and study designs to use ctDNA in our daily clinical practice for kidney cancer patients.

When it comes to biomarkers, KIM-1, kidney injury molecule-1, is a really promising biomarker, and we are very excited about it in kidney cancer. Previously, its prognostic role in the metastatic setting and its use for predicting disease recurrence in the adjuvant setting were shown in different studies. Now, at ASCO GU 2025, Dr. Wenxin Xu from Dana-Farber Cancer Institute presented the results of baseline KIM-1 and decreasing KIM-1 levels with treatment in the CHECKMATE-214 trial, involving patients receiving the Opdivo plus Yervoy combination.

Based on the results, if we see a good response in KIM-1 levels in the third week of treatment, we can say that the prognosis is good with Opdivo plus Yervoy treatment. However, if we don't see any response, can we say that the prognosis is poor, and should we change or intensify our treatment with other regimens or combinations? The results are promising, but we need more data and prospective evaluation of these findings in a clinical trial to make decisions about treatment selection and intensification.

This transcript has been edited for clarity and conciseness.

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