Panel Shares Thoughts on RCC Data: CheckMate 914, 214 and IMDC Selection Criteria

A roundtable discussion, moderated by Rana McKay, MD, discussed the latest updates in frontline treatment for renal cell carcinoma, including how data from the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024 alters the treatment paradigm. Dr. McKay was joined by Nizar Tannir, MD; Hans Hammers, MD; and Katy Beckermann, MD.

In the fourth segment of the roundtable series, the panel swapped opinions on data pertaining to CheckMate 914, CheckMate 214, and IMDC selection criteria.

Watch the next segment in this series.

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Dr. McKay: I love the introduction of CTLA-4. Dr. Beckermann, you alluded to it as well. Other studies have been conducted in this space. Why are those studies negative? Dr. Motzer presented data from CheckMate 914, a study examining adjuvant nivo/ipi. What led to the trial’s negativity? We were all optimistic, but unfortunately, it yielded negative results. The updated data from the nivolumab arm was grossly underpowered to show a significant difference. What are your thoughts on the landscape?

Dr. Beckermann: It is likely multifactorial, but the main point that stands out to me, even in positive studies, is our uncertainty in patient selection. It is possible that lower-risk patients were enrolled. Other factors, such as the duration of treatment, could also play a role. But ultimately, it comes down to patient selection. Some underlying biology may enable certain patients to respond to immunotherapy, leading to differing outcomes in studies like Keynote-564 and Checkmate 914.

Dr. Hammers: I completely agree. We have conducted multiple studies with nivolumab and pembrolizumab in the metastatic disease space, with no discernible difference between the agents. Patient selection is crucial. Keynote-564 succeeded because it selected the highest-risk patients. For studies focusing on disease-free survival, selecting high-risk patients is essential to detect any meaningful signal.

Moving away from adjuvant therapy is imperative. It is inefficient and costly, with many patients not requiring therapy. Instead, we should focus on identifying patients at the highest risk of recurrence, possibly through methods like circulating tumor DNA. By targeting minimal disease space, we can intensify therapy for those who truly need it.

Dr. McKay: Indeed, biomarkers remain a challenge. RCC presents unique difficulties due to less sensitive assays. Nonetheless, patient inclusion criteria, such as T1 patients and exclusion of M1 patients, and the duration of treatment, are crucial factors to consider. The threshold to stop therapy in the adjuvant setting differs from metastatic disease, as Dr. Motzer noted.

Dr. Hammers: Time may not be as critical as we think. The presence of tumor-reactive T-cells is more relevant. Different patient populations may respond differently to therapies like CTLA4 and PD-1 inhibitors. We should focus on intelligence studies and innovative designs like the MOTION trial.

Dr. Tannir: We still lack a reliable marker for identifying high-risk patients beyond clinical factors. The bladder cancer field’s progress with circulating tumor DNA is commendable. We should invest in similar efforts for kidney cancer.

Dr. Hammers: Agreed. We should intensify our efforts in identifying high-risk patients through advanced technologies like Path AI. These approaches offer a non-invasive means of assessing risk and response to therapy.

Dr. McKay: Path AI holds significant promise, especially in prostate cancer. Its application in predicting recurrence and treatment response is remarkable. We need to leverage such technologies to enhance patient care.

Dr. Tannir: Transitioning to frontline therapy, the long-term follow-up data from Checkmate 214 is encouraging. The rigorous assessment of response and PFS by independent committees is commendable.

Dr. Hammers: When administering nivo/ipi, close monitoring for toxicity and early intervention are crucial. Adaptation of protocols to obtain scans earlier in symptomatic patients can prevent missed opportunities for alternative therapies.

Dr. Tannir: Absolutely. Early intervention based on clinical symptoms and imaging findings can improve outcomes and facilitate second-line therapy if needed.

Dr. Beckermann: Patient education is key, especially regarding the potential for delayed responses with nivo/ipi. Managing patient expectations from the outset can help alleviate concerns about initial scan results.

Dr. Hammers: Indeed. Setting realistic expectations with patients, akin to the marshmallow test, can help them understand the nuances of treatment response.

Dr. McKay: The data from Checkmate 214 underscores the importance of upfront IO/IO therapy, particularly in favorable-risk patients. We need to ensure this information reaches community physicians and influences guidelines.

Dr. Hammers: Exactly. IMDC criteria for selecting patients for immunotherapy may need reevaluation. The OS benefit seen in good-risk patients treated with nivo/ipi highlights its efficacy in this population.

Dr. Tannir: Incorporating this evidence into guidelines is crucial. Insurance decisions should not hinder patients’ access to effective treatments.

Dr. Hammers: Agreed. We must advocate for guideline revisions to reflect the latest evidence. Collaboration between academic centers and community oncologists is essential to ensure the optimal delivery of therapies like nivo/ipi.

Dr. McKay: Patient education remains paramount, especially regarding expectations for treatment response. Empowering patients with accurate information can improve their treatment experience and outcomes.

As we move forward, future frontline studies must include favorable-risk patients to avoid excluding this critical population.