Personalized RCC Care: Decreasing Overtreatment, Identifying Cured Patients in the Adjuvant Setting

A roundtable discussion, moderated by Katy Beckermann, MD, PhD, discussed the treatment sequencing, management, and future directions of advanced or metastatic kidney cancer, as well as relevant clinical trial data from the 2024 American Society of Clinical Oncology Annual Meeting. Dr. Beckermann was joined by Yousef Zakharia, MD; Pavlos Msaouel, MD, PhD; Benjamin Maughan, MD, PharmD; and David McDermott, MD.

In the fourth segment of the roundtable series, the panel shares the advances, challenges, and future directions in frontline IO-based treatments for kidney cancer, emphasizing the need for better patient selection, biomarkers, decreasing overtreatment, and identifying cured patients in the adjuvant setting.

View the next segment on Improving Outcomes in Patients With Chromophobe, Papillary RCC.

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Dr. Beckermann: To wrap up our conversation on frontline IO-based treatments, does anyone have exciting insights from this meeting or recent developments over the past year? We have discussed COSMIC-313 and its challenges with triplet toxicity, but what do you all think are the most promising avenues for increasing cure rates, deep responses, and treatment duration?

Dr. McDermott: I think adjuvant PD-1 could have the biggest impact on cures, as it shows improvements in disease-free and overall survival, potentially reducing kidney cancer deaths. However, we need to better predict recurrence and who will benefit from treatment, as we are overtreating many patients, especially in the adjuvant setting where surgery alone cures 60% to 70% of patients. This overtreatment leads to significant costs and toxicity, including life-altering side effects for patients who might have been cured without the drug. In the adjuvant setting, the risk-benefit of IO is inverted, making it crucial to limit these drugs to those most likely to benefit.

Dr. Maughan: So you are saying the main issue is our inability to select the right patients?

Dr. McDermott: Yes, it is both predicting recurrence and managing overtreatment toxicity. We need better tools to identify who will benefit and who will suffer from side effects. Some promising data from this meeting on blood biomarkers and predicting who might recur is a step in the right direction. We must encourage this work to avoid unnecessary toxicity and improve patient outcomes.

Dr. Zakharia: It is great that we have the tools to treat our patients, but we lack biomarkers to guide us in selecting the right treatment for each patient. Some data presented at this meeting is promising, but we are still far from personalized medicine, which is much needed to avoid overtreatment and associated toxicity.

Dr. Maughan: I am also looking forward to the biomarker talks, particularly on the KIM protein and proteomics for patient selection. The concern about adjuvant treatment is real, as the absolute improvement in overall survival mirrors the harm these treatments can cause. It is a challenging discussion with patients who are worried about recurrence.

Dr. Beckermann: There is a lot of excitement around biomarkers, and I share that passion. While it is commendable that trials are publishing correlatives after 5 years, we need to push for prospective designs to better understand who is not responding and how we can de-risk treatments. This is crucial, especially in the adjuvant setting, where our goal is to cure patients while minimizing risks.

Dr. Maughan: Reflecting on the abstracts presented, the tremendous success we have had is evident. When I started years ago, median survival was about 9 months with high-dose IL-2 and interferon. Now, with better tools, we can explore novel combinations and use biomarkers to guide treatment selection based on individual biology. The explosion of options and evidence for HIF-2 alpha’s usefulness is incredibly exciting.

Dr. Beckermann: Adding to that, the advancements in our technologies and drug development have allowed us to explore other subtypes of kidney cancer and understand how current frontline treatments affect them in a more biologic way.