Nivo-Rela vs Nivo-Ipi: What 4-Year ITC and Real-World Data Tell Us About Treatment Selection
Panelists discuss real-world evidence comparing immunotherapy combinations for metastatic melanoma, highlighting retrospective analyses showing similar efficacy between nivolumab plus relatlimab and nivolumab plus ipilimumab, while emphasizing the relatlimab-based regimen’s lower toxicity and the need for individualized treatment decisions in patients who fall outside typical clinical trial populations.
The panel continued by addressing how immunotherapy combinations perform outside of clinical trials, emphasizing the importance of real-world data. Clinical trials like CheckMate 067 and RELATIVITY-047 enrolled highly selected patients with favorable characteristics—stable brain metastases, normal labs, and good performance status. However, many patients seen in everyday practice don’t meet these strict inclusion criteria. To evaluate outcomes in this broader patient population, real-world retrospective analyses using datasets such as Flatiron were conducted to compare the effectiveness of nivolumab plus relatlimab versus nivolumab plus ipilimumab.
These real-world studies used statistical adjustments to balance differences in baseline characteristics, attempting to replicate the rigor of randomized trials by using inverse probability treatment weighting. This approach aimed to control for the fact that clinicians may have chosen one regimen over another based on factors not always fully captured in data, such as frailty or comorbidities. Findings presented at ASCO showed that progression-free survival and overall survival were similar between the two combination regimens, even outside the controlled environment of clinical trials. Additional retrospective analyses from other institutions supported these results, reinforcing the notion that both combinations are viable options in standard oncology practice.
Despite comparable efficacy, toxicity remains a key differentiator. Ipilimumab-based combinations consistently show higher rates of severe side effects compared to the relatlimab-based regimen. This makes the latter an attractive option for patients who may not tolerate aggressive treatment well. However, without head-to-head randomized trials, choosing between the two remains nuanced and dependent on individual patient characteristics. The discussion concluded by acknowledging that while both combinations are strong contenders, treatment decisions must also factor in specific clinical situations, such as brain metastases, which were set to be explored in the next part of the session.
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