Nivolumab Plus Ipilimumab vs Chemotherapy in Unresectable Mesothelioma

PracticeUpdate: Could you elaborate on the trial presented at ESMO discussing the therapy option for unresectable mesothelioma?

Dr. Henry: LBA 65, a late-breaking abstract entitled "First-line nivolumab plus ipilumumab (Nivo plus Ipi) versus chemotherapy for unresectable malignant pleural mesothelioma." So not non-small but mesothelioma. This is CheckMate 743, an update—a three-year update. So it's been presented before three years, update. Primary endpoint was overall survival. Now a very interesting thing they did in this study is they looked for inflammatory marker expression. They had four genes and I'll name them, CDBA, PD-L1, STAT1, LAG-3, L-A-G three. They coded you as being high (all four) or low (none of the above), or just one. Three-year follow up, Nivo plus Ipi overall survival benefit was strong, a hazard ratio of .75 (significant), for the high, so, if you were the all four of those biomarkers positive, inflammatory, you had a 21.8 versus 16.8 month overall survival.

PracticeUpdate: Are there any safety concerns of the combination being evaluated in the CheckMate 743 trial?

Dr. Henry: The Nivo + Ipi combination which we've used in other areas—famous for melanoma—is not as significant side effect of these immune checkpoint inhibitors giving off-target effects, lung toxicity, skin, bowel, liver. So we need to watch for that, these need to be fairly well-off patients with performance status 0, 1, maybe 2. So what this says to me is while we have a platinum-based chemotherapy for malignant pleural mesothelioma which can work, this might be a better option and did a little better in this study than the base chemotherapy combination. So that brings immunotherapy once again to the forefront, especially if you enrich your population with these biomarkers.