Immunotherapy for NSCLC leptomeningeal disease? - 1271093

leaf
Posts:2

Hi,

My 72 year old mother (non-smoker) was diagnosed with stage 4 NSCLC adenocarcinoma 3 years ago. She has been treated with chemo: pemetrexed/carboplatin then pemetrexed/carbo/avastin then carboplatin/taxol. During this time, she has had some periods of stability (including a wonderful year without progression following the first pemetrexed/carbo) but there have been times of rapid spread from the original pleural tumours to the breast (which we understand is very unusual for lung cancer) and bones, for which she has had quite extensive radiotherapy.

In recent days, an MRI has shown leptomeningeal spread around her brain and base of spine. On searching the GRACE website, I have very much appreciated Dr West's frank and informative insights on this terrible condition.

My mother is currently having WBR and spinal radiation in an effort to stop the progression. Her oncologist is then willing to try pembrolizumab, which had been our original plan for when progression occurred following the last chemo. However, I have been unable to find any information on the effects of pembrolizumab in the presence of the dreaded leptomeningeal spread. Does anyone have experience or knowledge of this? I would very much appreciate any insights or advice on whether this is worth trying, even if very uncertain. Many thanks!

My second question is whether the pulsed tarceva treatment that Dr West and Dr Weiss describe in other posts might be useful to consider even though my mother was EGRF negative at initial diagnosis (is it possible that the EGFR mutation may emerge as the disease develops or that the tarceva may help her even in the absence of this mutation?).

This is a very difficult path to be on. Thank you so much for any insights or suggestions.

Forums

JimC
Posts: 2753

Hi leaf,

Welcome to GRACE. I am very sorry to hear of your mother's diagnosis, especially with regard to LMC. As you may see from my signature below, I have personal experience with this condition. My wife was EGFR positive, but pulsed Tarceva did not seem to help her. On the other hand, her cancer was rapidly progressing elsewhere, so Tarceva had probably just become ineffective for her in general. She had a suggestion of LMC on an MRI, but did not have a spinal tap to confirm the diagnosis, as her symptoms made that unnecessary.

That would lead to my first question, whether your mother is showing any of the typical symptoms of LMC - confusion, headaches, balance issues, focal weakness, double vision, etc. Although I do not want to create false hope, if she does not develop symptoms it is possible that the imaging does not actually show LMC.

I don't know of any specific evidence that immunotherapy in general or pembrolizumab in particular is effective against LMC. There's also not much to suggest that pulsed Tarceva would help in the absence of an EGFR mutation, although it can help (to a lesser extent) lung cancer patients without such a mutation. It's not likely that an EGFR mutation would develop after initial diagnosis, although it could have been missed in testing.

If your mother is feeling fit enough to tolerate more treatment, then pembrolizumab could certainly be tried.

My heart goes out to you as you deal with this, and I wish you and all your family strength, peace and comfort.

JimC
Forum moderator

leaf
Posts: 2

Hi Jim,

Many thanks for your very kind and informative response. I am so sorry to hear of the loss of your wife to this terrible illness.

Unfortunately my mother is starting to display some symptoms including balance issues and headaches (though still fairly mild), so it is probably a fairly conclusive diagnosis in her case. She has maintained a good level of fitness and activity throughout her illness, despite the many challenges placed on her body and I believe she is currently fit enough to tolerate treatment. She understands the seriousness of her diagnosis but would love to try something, even if with only a small hope.

I have noticed that the trials of immunotherapy in lung cancer exclude (always?) people with this condition. Do you know if the reason for this? I would appreciate any insights and also whether anyone else in this community has knowledge of someone with leptomeningeal disease who has tried pembrolizumab or similar.

It seems there may have been some success using immune therapy for patients with melanoma who have this complication (www.curemelanoma.org/research/mra-research-awards/team-science). Also there is a trial for melanoma patients that includes those with leptomeningeal spread (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367026 ). This has raised my hopes a little, but I have been unable to find any discussion of use of similar drugs in lung cancer patients.

Thanks, for your comments on EGFR. At this stage I do not think it would be fair to impose additional surgery but perhaps I should check whether any previous biopsies can be retested?

Unless someone advises us strongly to the contrary, or has other suggestions, perhaps it is best for us to try the pembrolizumab. We know there is great uncertainty but we are just trying to find a way to give her a chance without imposing treatments that may cause significant further harm to her quality of life while offering no chance of success.

Many thanks

catdander
Posts:

Hi leaf, I'm so sorry your mother has this horrible disease. The reason for no testing in lung cancer for immunotherapy and lepto or even brain mets is because they are still trying to get data only on the easier to treat (comparably speaking) non brain mets systemically. If brain mets and lepto were added to the group being tested it would bring down the efficacy numbers for everyone and a large number of people could miss out on effective treatment.

Please let us know how your mother does and I hope we hear some good news. Do you know if the research with immunotherapy on melanoma brain mets or lepto are getting any good results? While almost always different I would be interested in knowing.

All best,
Janine