News from ASCO: "Drug is first to help patients with melanoma of the eye"

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6/1/2013 10:57am
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New research focused on ocular melanoma is being presented today at the American Society of Clinical Oncology (ASCO) meeting-- research showing the first systemic treatment to have an impact in metastatic uveal melanoma... here are a couple links to articles about the research that came out today at the ASCO meeting:

http://www.reuters.com/article/2013/06/01/us-cancer-melanoma-eye-idUSBRE...

http://www.usatoday.com/story/news/nation/2013/06/01/melanoma-drugs-exte...

 

Warms Regards,

Sara - CURE OM

Very interesting; thanks.  This was actually one of the clinical trials we had been considering early this year, but my father's mel specialist warned him away generally from Phase II trials targeting uveal melanoma.  He said that because OM patients are a relatively small cohort, any Phase II trial targeting OM will not be using the "latest and greatest" drugs.  Drug companies will generally follow the money and only get around to testing for OM after first running trials for diseases with larger patient populations.  About this trial in particular, he said, "Oh, that uses an older MEK inhibitor.  We will be running a trial with a more advanced, next-generation MEK inhibitor later this year."  

We ended up going the anti-PD1 route, although we are currently in that nervous period between having signed the consent and undergoing final tests to make sure he qualifies.  If this doesn't pan out for one reason or another, the next step will probably be a MEK inhibitor.  So the question will be-- do we try selumetinib, which has been shown to have some effect though no silver bullet, or do we try for one of the "advanced" MEK inhibitors, which might be better or might do no good at all? Each trial of course excludes anyone who has ever taken another MEK inhibitor, so you only get one shot!  

Hi,

1) Which one is that new MEK-inhibitor your doctor (what's his name?) is expecting to make available in a trial? It is worth knowing that to judge his assessment.

2) If your husband has an advanced metastatic uveal melanoma he can't afford to wait months for the newest and latest, while not trying anything. Every minute counts with this disease. Doing an anti-PD1 in the menatime makes sense. If, after that you still have to wait for teh newest MEK inhibitor, it may well not be wise to wait.

3) Doesn't the Sloan Kettering study get contradicted by the MD Anderson study from Aug 2012 that says that MEK-inhibitors on their own do not have much therapeutic effect with GNAQ/GNA11 mutations, while a combo approach with MEK plus PI3K inhibitors works? See http://www.ncbi.nlm.nih.gov/pubmed/22733540

 

Peter L in Leiden, Netherlands (formerly in Windham, NH)

Hi Peter,

It's Dr. Daud at UCSF; I think he was referring to MEK162 in NCT01801358, although that trial no longer mentions SF as a possible location.  My father discovered his metastatis before the primary, and his ocular tumor is extremely atypical, meaning flat and small.  One ocular oncologist says it's definitely uveal melanoma, another says it's 'likely' uveal melanoma.  It metastasized to his skull first, more recently his liver and other bones.  Absolutely we made a decision to go for the low-hanging fruit in anti-PD1, since it hasn't been shown to be ineffective in OM, and the side effects are generally manageable.  Everything is taking longer to get started than we had anticipated, however.  He's also had one dose of ipi while we were waiting for the anti-PD1 trial.  Thanks for the citation; I am not familiar with the literature on MEK.  I will look into it.  He hasn't been tested for GNAQ/GNA11 yet.

Tami

Tami,

Just in case you did not know, f you need to figure out what trials are available, the CollabRx site is teh best to search on. It also allows for looking for the mutation that needs inghibiting, before you choose the trial. Overall it is an easier interface. You can also search by drug.

See for MEK 162 http://therapy.collabrx.com/melanoma/drug/MEK162 and

in general for GNAQ mutations: http://therapy.collabrx.com/melanoma/lookup?results_3.2

Also useful is thsi site which keeps track of developments in molecular biology and corresponding treatments (it is reasonably up to date, although not perfect, so one need to cross match):

http://www.mycancergenome.org/content/disease/melanoma/gnaq/102

As you can see, MEK inhibitors are usuable for a limited type of OM patients (about 50%), not all. So it is wise to have a biopsy and genetic assessment done asap.

I would not wait till USCF/SFO has anything. It is not like it is one of main players for OM treatments. MD Anderson, Jefferson Kimmel and Sloan Kettering are specialized in that. In fact, I do not see any major OM publications by Dr Daud either. he seems more into skin melanoma, a different beast. For example: his publications on inhibiting BRAF mutations are typically skin melanoma studies as BRAF doe snot play any rol of significance in OM.

 

Peter L in Leiden, Netherlands (formerly in Windham, NH)

Tami,

Just in case you did not know, f you need to figure out what trials are available, the CollabRx site is teh best to search on. It also allows for looking for the mutation that needs inghibiting, before you choose the trial. Overall it is an easier interface. You can also search by drug.

See for MEK 162 http://therapy.collabrx.com/melanoma/drug/MEK162 and

in general for GNAQ mutations: http://therapy.collabrx.com/melanoma/lookup?results_3.2

Also useful is thsi site which keeps track of developments in molecular biology and corresponding treatments (it is reasonably up to date, although not perfect, so one need to cross match):

http://www.mycancergenome.org/content/disease/melanoma/gnaq/102

As you can see, MEK inhibitors are usuable for a limited type of OM patients (about 50%), not all. So it is wise to have a biopsy and genetic assessment done asap.

I would not wait till USCF/SFO has anything. It is not like it is one of main players for OM treatments. MD Anderson, Jefferson Kimmel and Sloan Kettering are specialized in that. In fact, I do not see any major OM publications by Dr Daud either. he seems more into skin melanoma, a different beast. For example: his publications on inhibiting BRAF mutations are typically skin melanoma studies as BRAF doe snot play any rol of significance in OM.

 

Peter L in Leiden, Netherlands (formerly in Windham, NH)

I had bookmarked the CollabRx site months ago, but hadn't looked recently.  Thanks for the reminder!  The interface really is easy.  It's odd that it recommends nivolumab but not lambrolizumab, though.

Tami,

 

PS:

Personally I would not just focus on MEK inhibitors solely, but on a combination of MEK inhibitors and PKC inhibitors, which is what that trial is about that you mentioned. IT is not only a MEK trial. There is some research with OM that shows that the MEK inhibitor enhances the effect of the PKC inhibitor.

See the Jan 2012 study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257235/

Also make sure to look at Delcath's Chemosat as a last resort treatment. It offers impressive survival rates with OM. Not all big clinics offer it, bexcaus ethere is a dispute with the FDA going on, but soem do and you can apply then for 'compassionate use' till it gets fully approved.  Don't underestimate this option, especially for helping in advanced cases. In Europe and Australia it has already bene approved and in the USA it was originally semi-apporved but teh FDA changed the rules of the game last minute. It has minor side effects (big plus!) and can be repeated every 4-6 weeks. See results of trial Phase III (NCT00324727)

Peter L

Thank you very much, Peter.  I think I still have a lot of research to do.  By the way, since you seem on top of things, do you happen to have an opinion on the Genentech ADC DEDN6526A (trial NCT01522664)?  Fifth-hand rumor has it that it is working well on OM patients... two, anyway.  

http://forum.melanomainternational.org/mif/viewtopic.php?f=54&t=34242

I'd saved the CollabRx site several weeks ago, but had not looked lately.  Just indication!  The interface is simple.  It's odd it suggests nivolumab although not lambrolizumab, though.