Thread by @EvanHallMD

With one day for the dust to settle, here are my thoughts on some of the #ASCO21 #melanoma data.
1) It is interesting to me that no adj PD-1 melanoma study has yet shown OS benefit vs comparator arm (CM238 - nivo vs ipi, S1404 - pembro vs HDI or ipi, KN054- pembro vs placebo).

Is this because more time in f/u is needed to see diffs emerge? Or does it suggest that PD-1 is equally effective regardless of disease setting (adj vs metastatic) and that enough pts with metastatic melanoma have durable long-term control on PD-1 to explain lack of OS benefit?

I suspect that PD-1 does cure some melanoma pts in the adjuvant setting. But are these the same pts that would have been cured in the metastatic setting? Not easy to answer but longer f/u of these three pivotal studies will be very important.

2) Interesting data from RELATIVITY study of #relatimab presented by @evanlipson. PFS improved while most importantly, toxicities did not seem much higher than with nivo monotherapy. The toxicity profile seems to compare favorably to ipi/nivo.

Looking forward to ORR, OS data. I could envision nivo/relatimab being a reasonable option for lower disease burden pts without brain metastases.

Also, neoadj data presented by Dr. Amaria @MDAndersonNews was quite interesting and compelling with consistent message of lower tox than expected with ipi/nivo. Would like to see nivo/rela vs ipi/nivo studied head-to-head in neoadjuvant setting.

3) #TIL continues to show that a subset of patients experience long term disease control. My question is how we would implement this if it became available tomorrow. This would not be widely available and would likely be offered by centers with expertise in cellular tx.

How will we ensure that all patients have equitable access to this promising but labor/resource intensive therapy?

4) Much less publicity, but also keen to see updated results of CM-511 (ipi 3 / nivo 1 vs ipi 1 / nivo 3) in metastatic melanoma presented by Dr. Lebbe. In my opinion, this is the most underrated study in melanoma over the past 5 years.

Study was designed for tox endpt rather than non-inferiority of efficacy, but it was a very large study (~360 pts). Nivo 3/ipi 1 dosing is clearly safer than nivo 1 / ipi 3. OS curves are nearly superimposable.

Aside from pts with brain mets, I think nivo 3/ipi 1 is very reasonable 1L metastatic option. It is also much less expensive for payers and health systems, just on cost of pharmaceuticals, let alone treatment of AEs, hospitalizations, etc.