Overall, no big surprises in Melanoma, unlike we had them in the last few years. Now it's rather drilling deep: how do we sequence therapies? Which patients are doing particularly well- or poorly- on which therapies? Can we minimise side effects? Nearly 200 posters to go through!
Brain mets remain the big challenge in Melanoma, so it was encouraging to see that Ipi/ Nivo also works in untreated brain mets and that better than Nivo alone. It is worth going through the next two abstract in details as the 2 studies are looking at different groups of patients- untreated brain mets, treated but locally progressing brain mets, lepto-meningeal disease
Pts with asymptomatic melanoma brain mets with no prior local brain therapy were randomised to cohort A (nivo 1mg/kg + ipi 3mg/kg, Q3W x4, then nivo 3mg/kg Q2W) or cohort B (nivo 3mg/kg Q2W). Cohort C (nivo 3mg/kg Q2W) had brain mets 1) that failed local therapy (new +/- progressed in previously treated met), 2) were neurologically symptomatic and/or 3) with leptomeningeal disease. Prior BRAF inhibitor (BRAFi) was allowed.
From a historic perspective, this is important as patients with brain mets were first routinely excluded from clinical trials, so it took way too long out to find out whether these drugs also work in the brain. And that in a disease known for its unfortunate property to metastasise to the brain!
Question remains: if you had one or only a few lesions in the brain, would you want to take the risk to be treated with Ipi/ Nivo, fully knowing it does not work for everyone? Or rather get SRT (stereotactic radio therapy), just to make sure? Different case for many, many (miliary) mets- this could help avoid whole brain radiation that is widely feared due its long-term impact. So an important step!
Adjuvant treatment is a tempting concept but with the current level of side effects, the big question will be whether it improves overall survival and not only progression-free survival.
How to overcome resistance to immune therapy has become the next big topic after the initial excitement over immune therapies. Priming the body with higher levels of antigen- giving T-cells more material to train on- by e.g. intra-tumoral injections (like T-Vec, or HF10) or improving the environment for T-Cells (like IDO), both in combination with checkpoint inhibitors are currently tested approaches. Another topic is how the microbiome of the gut affects the response to immune therapy.
Financial toxicity was at the forefront of any discussion- a large change from only very recently. Several times, people stood up after a presentation and asked: I have a patient with x, you said I should give y, but what do I do as I have no access to y? Hitting home the message that progress without access is meaningless.