Jeffrey S. Weber, MD, PhD, discusses updates related to melanoma practice and care from ASCO 2023.
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The amazing thing was that in this PD-1–LAG-3 trial, the response rates were fantastic. The response rates in the initial and in the second cohort, each of about 40 patients, were very high: 63% in both of those cohorts as evaluated by the investigators. You even had a 56% response rate in the PD-1–experienced cohort that had negative prognostic factors like liver metastases or prior brain metastases.
If you look at the toxicity, the grade 3, 4, or 5 immune-related adverse events are only about 13%, which is not much more than you would expect with the PD-1 antibody alone; although interestingly, it looked like there were, relatively speaking, more endocrinopathies. If you look at the distant metastasis-free survival by stage, we're looking at 86 vs 78 for the IIB disease and 80 vs 68, which again, is a pretty healthy difference at 36 months, for those who have IIC disease. The hazard ratios were 0.62 or 0.57, respectively, which again, I think are very nice and would suggest that there's clear benefit for adjuvant pembrolizumab in resected stage IIB and IIC melanoma.
We now have updated PFS data, which still show a significant separation. The hazard ratio is 0.81, and the projected 36-month absolute difference in PFS was 31 vs 27 with follow-up that's now at about 25.5 months. Again, the median PFS was reached at the initial assessment, which led to the registration of nivolumab-relatlimab for patients with metastatic unresectable melanoma, and that was 10.2 vs 4.6 months. Those medians haven't changed.
Points to remember for the RELATIVITY-047 update are that all of the outcomes examined still favor the combo vs nivolumab alone; the PFS hazard ratio is 0.81; the 3-year PFS rate is 31 vs 27; the overall survival now, for the first time, hazard ratio is documented at 0.82. The 48-month survival of 52% for the combo is clearly superior to 42% for nivolumab alone.