Acquired Resistance to alectinib alecensa ALK positive - 1293854

lessie
Posts:22

Hello, in watching the videos on acquired resistance with ALK + targeted therapies, there was one where Dr. Alice Shaw spoke, whereby she was mentioning some of the ALK+ genomic alterations and which drugs are not effective for certain mutations, and certain drugs that were. Recently my biopsy was sent to Foundation for molecular testing and came back ALK+ EML4-ALK fusion, "L1196Q". I was hoping that the report from Foundation would pinpoint which targeted therapies would be effective for this specific ALK+ genomic alteration, but is just listed the ALK+ inhibitor drugs Alectinib, Crizotinib, Brigatinib, Ceritinib. I have been on Alectinib for a year and a half, and crizotinib for 14 months before that. Recent progression to mediastinal lymph nodes causes my oncologist to suspect acquired resistance now to alectinib.

Is there any way to find out which targeted therapy drug listed in the report would be the correct therapy for the specific alteration identified?

(This month marks my 4 year survivor anniversary and I look forward to many more.)

Thank you.

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Reply # - January 23, 2018, 12:46 AM

beeg2017
Posts: 11

Lessie, I was watching a YouTube video of Alice Shaw where she had a slide of resistance mutations and which drugs are not effective against them. The slide show that crizotinib is not effective against L1196Q but Ceritinib, Bigatinib and Alectinib are effective against this mutation.

Reply # - January 23, 2018, 09:07 AM

JimC
Posts: 2753

Hi lessie,

Although I was able to track down some of the other ALK variants, I have been unable to find anything on the specific mutation to which you refer. Unfortunately when you get to this level of specificity in the context of relatively new drugs, there doesn't tend to be a great deal of data.

JimC
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Reply # - January 23, 2018, 09:19 AM

catdander
Posts:

Hi Lessie,

I'm not sure what discussion of Dr. Shaw's you're referencing but it appears the topic is a work in progress.

This video from post 2017 ASCO round table discussion is an excellent conversation about sequencing of treatments for those who are ALK positive. They discuss the possible differences in the subsets of ALK you're asking about but say they only suspect a difference in efficacy but it's not fully studied or known yet what's what. So they give some hypotheticals of sequencing that I think will be helpful in your planning. https://www.youtube.com/watch?v=WVoq4GE1yVI&feature=youtu.be

You may have seen these videos of the recent targeted therapy patient forum. They are filled with excellent info though you need to wade through them because they are unedited.
http://cancergrace.org/lung/targeted-therapies-in-lung-cancer-patient-f…

Something you probably know but I'll say anyway is I it's not necessary to move on to another treatment with only slight progression. It's often possible to get more out of a targeted therapy even after slow progression.

I hope this helps,
Janine

Reply # - January 23, 2018, 10:15 AM

catdander
Posts:

You wrote you had L1196Q but I've not seen that in Dr. Shaw's discussions. Did you mean L1196M?
L1196M appears on the slides Dr. Shaw uses when describing resistance mutations. At 1 hr. 14 min she shows a chart suggesting L1196M occurs with alectinib and ciritinib which. Brigatinib doesn't show that mutation. If I'm understanding right brigatinib would be a good next option and the newer gen loratinib will be waiting in the wings. How exciting is that?

Slow an steady is the game and I hope you get more out of the alectinib before moving on.

Reply # - January 24, 2018, 05:48 AM

JimC
Posts: 2753

Yes, I had seen the information on mycancergenome.org but as beeg2017 states, there is nothing on L1196Q, on that site or anywhere else that I could find.

JimC
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Reply # - January 24, 2018, 07:47 PM

lessie
Posts: 22

Thank you Jim, Janine and Beeg,
Yes, it is L1196Q, and I did not see it mentioned in the video presentations. Apparently this variant does, however, exist, I did a search on Google Scholar and it was mentioned in a scientific paper which was beyond my scope of understanding. Maybe it's the same "family" as the L1196M. Thank you all for providing the links and resources. Beeg and Janine I appreciate the info and the time stamps!! Yes, it is very exciting to have drugs out there already in the wings. Jim, I agree, "when you get to this level of specificity in the context of relatively new drugs, there doesn’t tend to be a great deal of data". The oncologists probably have access to databases that are more specific than what we have access to. Even Watson! Thanks to all.

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