If a BRAF-mutated melanoma patient developed metastatic disease progression on adjuvant anti-PD-1 monotherapy, do you recommend switching to BRAF/MEK targeted therapy or combination immunotherapy?

The developing pre-clinical and clinical data is clear on this and I believe it becomes even more clear with time. While the DREAMseq study did not enroll patients following adjuvant therapy as the patient in the case, the overall evidence clearly shows that BRAF/MEK inhibitor resistant melanomas ar...

I think the time frame from the end of adjuvant treatment to disease progression is important to consider as well. The SITC immunotherapy resistance guideline (Kluger et al., PMID 36918224) is defined as recurrence <1 year. If the recurrence occurs >1 year post adjuvant IO, you can still re-challeng...

As mentioned by Dr. @Dr. First Last, there is no data in this setting as DREAMseq didn’t include patients who progressed on adjuvant anti-PD1. In my opinion, it depends on the nature of the progression. If it’s rapid and you think you only have one shot at controlling the disease, I would choose BRA...

It goes without saying that a clinical trial is always preferred for such a patient. I follow certain rules when I see a patient progressing on anti-PD1. First, I get an MRI brain and PET scan to make sure that we have identified all the areas of progression. For those with brain progression, the be...

This is a great question and one that we don't have a definitive answer to. I tend to use BRAF/MEK when they have aggressive or high volume recurrence, ipi/nivo if a low volume/slow pace recurrence. I think you can make a strong argument for BRAF/MEK preferentially in these patients, given the high ...

As long as the patient is not rapidly progressing, I favor a combination of ipilimumab plus nivolumab in this setting. We know both from the SWOG 1616 study and data on pembrolizumab plus ipilimumab after PD-1 antibody-failure that the overall response rate in this setting is around 30%. Given that ...