Advice, please

I am sorry for what you are going through. I am not one of the board’s experts so dont really have the best advice.

That said your treatment plan seems reasonable. It may be that the ipi nivo works better than the pembro and also that it has had a chance to work on the latest recurrence, so then it becomes neo adjuvant – it has an idea what to target.

I know NRAS is perceived to be more aggressive but I am NRAS too and in my case it was not true – it just kept growing but slowly. For me adding TVEC to pembro made the difference – my recurences were alwaye local, seemingly no spread, so this could be another option. but it may be that adding ipi does the trick too.

Beyond this there are trials and treatments like TILs (not sure in the uk), but it seems your doctors are treating you quite aggressively, especially compared to other uk patients on this board (I am british too but work in the us). You seem to have good doctors but anither option would be to try to contact Royal Marsden who i think are among the best in the UK (I have heard of Dr James Larkin)

i am sorry about the repeated surgeries – i had to have two, and was heading for a third until the TVEC + pembro option worked. But for many of us on the board surgery plus immunotherapy has worked, so it can for you too

Good luck w your surgeries and treatment too

Mark

You are currently on the treatment with best chance of success (ipi/nivo) and the “palliative” designation is really just a turn of the phrase. This incredibly expensive treatment is in reality funded by the NHS because it can significantly prolong your life or even cure you. First thing you need is to try and finish the treatment. The treatment is harsh enough to add anything else in the process.

If the tumor regrows you sound like a candidate for TIL. This is because your tumor can be easily harvested and you have a lot of material there. I would try and ask your doctor about joining a TIL trial. This would likely be in London in your case. I think I have heard that they are looking at having some trials in the uk now (were previously delayed by Covid).

I disagree with you about star (or more specifically just good and creative) oncologist. Any doctor would more readily suggest treatment regimes that they and their team have access and experience with.  This will wary quite a lot between different doctors and centers. You have to keep in mind that medical profession is a field of work like any other -maybe think of it like fixing a car?

In any case – once you are treated by someone you will have to simply do what this person thinks best or find another doctor. The relationship between doctor and patient is not exactly an equal exchange of ideas. So eg if you think TIL is good idea try to figure out what your team thinks of possibly joining a trial and if they aren’t very proactive try a different doctor privately.

Good luck with whatever you decide!

So sorry that you are dealing with a repeat scenario.  I have no brilliant easy answers but here are my thoughts:

1.  Re: immunotherapy.  Sometimes anti-PD-1 as a single agent (no matter if Keytruda/pembrolizumab or Opdivo/nivolizumab) works wonders.  For other folks, the ipi/nivo combo is essential and far more effective.  So there is hope there for you.
2. Also in regard to immunotherapy:  Immunotherapy requires that you be patient with the patient.  In other words, it can take time.  Therefore starting it quickly is essential!  Not very comforting factoids when deep in the mire dealing with a resurgence of tumor – but…I think points 1 and 2 mean you still have hope of positive effect from your current treatment.
3. Surgery works.  To an extent.  Especially since we know that immunotherapy works best with the lowest possible tumor burden, cutting crap out immediately lowers that burden.  Research:  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2019/07/cut-it-out-prolonged-overall-survival.html
4. NRAS mutation – clearly a bit of a bear and obviously not news to you!  Here is the data that I have published. It might give you ideas to speak with your docs about if current treatment does not do what it needs to.  Scroll through for info ranging from 2015 to ASCO 2021:  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/search?q=nras
5. I am (and have been for many years) a huge believer in liquid biopsy of ctDNA.  It can tell us so much with so little invasion!!!  It can type our tumors.  Look for the existence of those nasty bits bobs in our blood.  Monitor the quantity of those bits to determine whether a therapy is working to annihilate those bits – or not – helping guide choice and duration of that therapy.  Anyhow – here’s tons of rants and data if you’re interested:  https://chaoticallypreciselifeloveandmelanoma.blogspot.com/search?q=ctDNA
6. As far as the International Super Heroes and Heroines of melanoma ~ Up front I will admit extreme prejudice for the Wizard Weber as he ran the phase 1 clinical trial of nivolumab that saved my life in 2010 combined with his incredible dedication to melanoma patients.  I have never known him to fail to get back to a melanoma patient (including those that are not ‘his’) to give his best advice, even if it is that the patient would be better served by treatment under someone other than himself.  Rare traits in humans and docs in my opinion.  BUT – the main benefit from ‘superstars’ to me are these:
   1. Two big brains are better than one, and if they can offer you and/or your doc their advice you have lost nothing and may have gained a great deal.
   2. Many of the locations ‘superstars’ land provide greater services in their area of expertise.   A symbiotic relationship that creates better facilities, more skilled ancillary staff (from laboratories, surgeons, nurses, etc), and more trial options.  This may turn out to be something of value to you or not.  You are correct that the facilities you mentioned in the UK are quite good and just now, I think you are pursuing the reasonable next step.  However, staying on top of your disease – as you are more than well aware – will be essential in determining your next best action.

Hope this offers some help and a great deal of hope.  Hang in there.  I wish you my best.  Celeste