The extended follow-up data from the phase 3 CheckMate 214 trial has sparked significant discussion among oncologists about treatment selection in frontline metastatic renal cell carcinoma (mRCC), with experts highlighting both the impressive long-term survival rates and the pressing need for reliable biomarkers.
Long-term Survival Outcomes
The 99-month follow-up data from CheckMate 214 (NCT02231749) demonstrates remarkable durability of response, with approximately one-third of patients still alive at nearly 10 years after treatment with the nivolumab plus ipilimumab combination. This outcome has particularly impressed clinicians for its potential curative impact in a subset of patients.
"The curve plateaus, and it looks like there's a decent percentage of patients likely being cured, if we can use the word cure," noted Dr. Vishal Rana, emphasizing the significance of these results for treatment selection, particularly in younger patients with lower disease burden.
Current Treatment Selection Challenges
Despite the encouraging long-term data, clinicians face significant challenges in selecting between dual immunotherapy (nivolumab/ipilimumab) and TKI/PD-1 combinations (such as cabozantinib/nivolumab). The lack of predictive biomarkers remains a critical limitation in treatment decision-making.
Dr. Shiven B. Patel highlighted this challenge: "Going back to the Kaplan-Meier curves, especially in favorable-risk disease, it seems that half of the patients benefit from ipilimumab/nivolumab, and half don't and maybe should get IO/TKI. We have no idea who those patients are on day 1 of clinic."
Emerging Biomarker Research
Progress is being made in developing predictive tools. Recent developments include Tempus's immune profile score technology, presented at the Society for Immunotherapy of Cancer Annual Meeting, which shows promise in predicting responses to single-agent PD-1 inhibitors. However, its applicability to combination therapy decisions remains uncertain.
Clinical Decision-Making Factors
In the absence of definitive biomarkers, clinicians currently base treatment decisions on several clinical factors:
- Disease burden and progression rate
- Symptom severity
- Patient age and overall health
- Tolerance for potential adverse events
Dr. Elie Fahed explained the rationale for choosing cabozantinib/nivolumab in certain cases: "I do it when I want to be sure I have as high a response as possible in patients with high-burden disease who are very symptomatic. Because if immunotherapy works, it's great, but you don't know that ahead of time."
Managing Disease Progression
The discussion also addressed the challenge of distinguishing true progression from pseudoprogression, which occurs in approximately 7-8% of RCC cases treated with ipilimumab/nivolumab. Clinicians emphasized the importance of considering multiple factors:
- Patient's clinical status and symptoms
- Laboratory markers including hemoglobin levels
- Timing and extent of radiographic changes
Dr. Andrew J. Pellatt noted, "My experience was it was usually maybe 15% to 30% growth at most. I would also think about the degree of progression. If the disease burden has doubled, I would be inclined to think that's not pseudoprogression, even if they feel well."
