Editorial Note: The ESMO Asia 2024 conference, hosted recently in Singapore, provided a platform for in-depth discussions on advancements in oncology. During the event, Urology Frontier had the opportunity to interview Dr. Jae-Lyun Lee, a leading oncologist from the Asan Medical Center at University of Ulsan College of Medicine in South Korea and the principal investigator of the Phase III LITESPARK-005 study. Professor Lee shared his insights on the latest strategies in managing advanced renal cell carcinoma (RCC), including key findings from the LITESPARK-005 study, challenges in accessing targeted therapies, and the importance of multidisciplinary care. He also reflected on his experience attending ESMO Asia 2024.Urology Frontier: What is the role of multidisciplinary team evaluations for patients with advanced RCC?
Dr. Jae-Lyun Lee:At my institution in South Korea, we have a dedicated multidisciplinary team for urologic oncology, which includes a focus on bladder cancer, upper tract urothelial carcinoma, prostate cancer, and RCC.
For advanced RCC, especially in cases of oligometastatic or locally advanced disease, collaboration across disciplines is crucial, as surgical resection often plays a pivotal role in the treatment process. However, in cases of widespread metastatic disease, particularly when systemic therapy is involved, input from a medical oncologist is typically sufficient to determine the optimal treatment strategy.
This approach has become even more relevant with the integration of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) into personalized treatment regimens. For example, the necessity of nephrectomy as a first-line treatment has decreased significantly. Multidisciplinary evaluations remain particularly valuable for patients with localized advanced or oligometastatic disease, where treatment planning is more complex.
Urology Frontier: Advanced RCC has entered the era of targeted therapy. According to the LITESPARK-005 study, belzutifan has shown significant benefits for patients with advanced clear cell RCC (ccRCC). How does belzutifan perform in Asian patients?
Dr. Jae-Lyun Lee:The findings from the LITESPARK-005 study demonstrate that belzutifan significantly improves outcomes in RCC patients. In the Asian subgroup, belzutifan achieved a high response rate of approximately 30%, including one case of complete response (CR). While the number of patients in the belzutifan arm was relatively small, the drug still showed superior response rates and longer progression-free survival compared to other treatments.
Belzutifan’s strengths lie not only in its efficacy but also in its tolerability and safety profile. While Grade 3 or higher adverse events were more common with belzutifan, the majority of these were manageable, such as anemia, which could be addressed through granulocyte colony-stimulating factor (G-CSF), transfusions, or temporary treatment interruptions. Importantly, less than 5% of patients discontinued treatment due to side effects.
The good tolerability of belzutifan has contributed to its inclusion in adjuvant and first-line treatment regimens. Although no overall survival (OS) benefit was observed in the intent-to-treat (ITT) population or the Asian subgroup during the LITESPARK-005 trial, this may be attributed to the availability of effective subsequent treatments like tivozanib, axitinib, or everolimus.
In Asia, major cancer centers offer access to clinical trials, and the availability of follow-up therapies may explain the lack of observed survival benefits in these studies. Nevertheless, the value of belzutifan is undeniable.
The primary challenge with belzutifan is its cost. Currently, the drug is only approved in the United States. I believe that belzutifan will be introduced in East Asian markets in the near future, but its high price remains a significant barrier. Although its toxicity risks are relatively low, the financial burden on patients is substantial. Efforts to improve access to new therapies like belzutifan are essential to address this issue.
Urology Frontier: How can we optimize treatment regimens in clinical practice to improve outcomes for ccRCC patients?
Dr. Jae-Lyun Lee:Available treatment options currently include ICI-ICI combinations and ICI-TKI combinations. For instance, pembrolizumab combined with axitinib, pembrolizumab with lenvatinib, and nivolumab with cabozantinib are all viable ICI-TKI options. Among these, pembrolizumab and lenvatinib have achieved a response rate of up to 70%.
Despite the high response rates and improved progression-free survival, achieving OS benefits remains a challenge. Ongoing clinical trials are exploring ways to enhance response rates and long-term survival through more refined treatment strategies.
When considering belzutifan, its tolerability makes it a preferred candidate for incorporation into treatment plans. However, determining the optimal scenarios for ICI-ICI versus ICI-TKI combinations is critical. In my practice, I generally favor ICI-ICI combinations for most patients due to their tolerability and reserve ICI-TKI regimens for those with advanced disease or poorer physical condition who may require alternative treatment approaches.
Urology Frontier: What are your impressions of attending the ESMO Asia 2024 conference?
Dr. Jae-Lyun Lee:The ESMO Asia conference is an excellent forum for bringing together oncologists from across Asia to discuss region-specific topics. This was my first time attending, and I was impressed by the outstanding organization of the event.
I look forward to participating in future conferences like this, as they offer a fantastic opportunity to connect with oncologists from all over Asia and share insights into advancements in cancer care.
Conclusion Dr. Jae-Lyun Lee’s reflections highlight the evolving landscape of advanced RCC management, with a focus on innovative therapies like belzutifan and the importance of tailoring treatment strategies through multidisciplinary collaboration. His insights into the challenges of accessibility and the potential of new therapeutic options provide valuable perspectives for optimizing patient outcomes in the region.
