Tawbi Discusses the Role of Brain Metastases and PD-L1 Status in Melanoma
Source: Targeted Oncology, September 2024
DISCUSSION QUESTIONS
- From the RELATIVITY-047 (NCT03470922) and CheckMate 067 (NCT01844505) trials, what are the most important efficacy and safety data?
- How do you select a specific immunotherapy (IO) regimen (i.e. nivolumab [Opdivo]/relatlimab [Opdualag] vs ipilimumab [Yervoy]/nivolumab)?
- How do you balance efficacy, safety, patient preferences, goals of therapy, and quality-of-life when recommending a first-line regimen?
Putao Cen, MD: There were fewer grade 3 to 4 adverse events with [nivolumab/relatlimab than ipilimumab/nivolumab in their respective trials];1,2 is that because RELATIVITY-047 was a later trial, maybe 10 years after ipilimumab/nivolumab, and physicians know how to foresee and prevent the severe toxicity? They stop the treatment or hold the treatment when they see grade 1 toxicity, for example, and they have a better second line with the BRAF inhibitor, and have more and better treatments, so maybe the survival is catching up compared with the ipilimumab/nivolumab trial conducted 10 years ago?
Hussein A. Tawbi, MD, PhD: Those are interesting points. I don’t think so. I think the toxicity is less purely based on mechanism for the LAG3 drug. I think the single-agent PD-1 [inhibitor] has less toxicity now than we had in phase 3 trials before. Usually it’s about 15% or 16%, and in this trial, it was 12%. I think…the experience is probably accounting for those few percentage points. The survival is not different because you’re comparing the 2 arms of it being of nivolumab/relatlimab vs nivolumab; you’re comparing them to the same post treatment regimens. We showed that in the poster I presented at the 2024 American Society of Clinical Oncology annual meeting and both arms of the study have the same amount of BRAF [mutations], same amount of ipilimumab/nivolumab in the second line, and there’s still a survival advantage.3 I think both the efficacy and the toxicity for LAG3 are mechanism based. I don’t think they’re just era related.