Expert perspective on the optimal selection and use of first-line therapy in patients diagnosed with metastatic melanoma in the context of the current treatment paradigm.
Sajeve S. Thomas, MD: I think for this specific patient, nivolumab and relatlimab is a reasonable option. Certainly with the elevated LDH [lactate dehydrogenase] ... it is a concern that the progression-free survival may not be as good with this combination. This was presented at ASCO [American Society of Clinical Oncology], where folks with elevated LDH didn’t have as good of a PFS as those with a normal LDH. This is something we’ve seen with prior PD-1 or ipilimumab/nivolumab, where folks with low LDH typically did a bit better in terms of overall survival. In this situation, I think it’s dealer’s choice ultimately in terms of doing PD-1 based therapies, whether you do PD-1 with rela or PD-1 with ipi. My decision-making in terms of deciding between doing ipi/nivo, for example, which I think is an easier decision if they have brain metastases, if they have a high burden of disease, if they look like they have a pending visceral crisis where we’re not going to get a second chance at doing this, then I might prefer ipi/nivo as the best chance for response, 50% to 55%. We know that’s the response rate we see with metastatic brain disease, and certainly for folks who are BRAF wild type, that would be the preferred option. If they’re BRAF mutated, they need response and they need it quickly, then I would tend to pick a BRAF MEK inhibitor combination first, and maximize my best response. Ultimately you can switch them over to ipi/nivo.
Outside of those indications, I think about what our goal of care is. I have folks who are deathly afraid of adverse effects, or folks who have autoimmune conditions, so in those situations I want to minimize any concern for toxicity as best we can. If the patient is going to give up on me, then we’re not going to get very far. In those situations, I think PD-1 monotherapy makes a lot of sense, and certainly we can escalate therapy if we’re not getting the best response. In those patients who respond with PD-1, whether it be nivo or pembrolizumab,which has a 30% to 40% response, you have a majority of those patients who do well long term and never need to see therapy again. The duration response was pretty good. For folks who didn’t respond, we’ll need to escalate the therapy to something different in those situations. So, a lot of immune concerns or safety concerns, PD-1 monotherapy makes the most sense.¼For folks with brain metastases, pending visceral crisis, high burden of disease, BRAF mutated, I think ipi/nivo. And then you’ve got everyone else in between, where I think nivo and rela is perfect for them.
With IL-2, the response rate was 1 in 20; with ipilimumab, the response rate is 1 in 5; with PD-1 monotherapy [we’re] having a response rate of 1 in 3. Whether we do ipi/nivo or ipi and rela, the response rate is roughly 40%, 50%, or every other patient we treat, practically. With that response rate, you can see there’s an escalation of maybe some adverse effect issues that we have to worry about with our patients.
Transcript edited for clarity.