Multiple EGFR mutation lung cancer

Hi happybluesun,  Welcome to Grace.   I'm sorry your mom is going through this. 

Driver mutations are mutations that drive (or cause) the cancer.  Having more than one driver mutation is quite rare and not well understood and may be where TP53 comes in.  That is why getting a consutation with someone at an academic institution that has a "molecular tumor board" will likely be the best place to put together the best plan for your mom.  Can a Patient Have Multiple Mutations & How to Treat?  is a video covering the topic. 

Tagrisso is the obvious current treatment for egfr exon 21 and that has been tried (3 months is usually long enough to see benefit but not absolutely always).  The other targic is exon 20 which has been more difficult to treat.  Here is a link to exon 20 search results from our video library; I'd stick to the videos created in the last year.  Specifically, Sunvozertinib shows great promise but isn't FDA or CDE approved. However, it was given a special designation in both China and the US that will/should help get to the answer about whether it is as good as it appears to be.  So while your oncologist can't prescribe it it may be worth looking into a trial.  Academic settings are also the best place to find appropriate trials. 

If you have questions about getting a 2nd opinion or consult this is the article to read.

I hope this helps.  If you have more questions don't hesitate to ask. 

Best of luck,

Janine

Hi happybluesun, How is your mom feeling?  Her case has specific components including the rare combo of mutations situation we can't help with a specific "this is standard of care".  She may be eligible for a clinical trial, local therapy, or the combo her docs have planned may be best. because of her rare set of mutations and lack of benefit from TKIs, it may make sense to try this triplet of treatments.  everything you need to know about targeted therapies...let me know if i can help

There is an issue with sequencing TKI after immunotherapy/CPI.  Often, people develop dangerous lung inflammation when taking TKI after they've taken immunotherapy.  We don't know why yet.  So it's best to use up all your possible TKI options before moving on to immunotherapy. 

The triplet of chemo, Bevacizumab, and tecentriq could work very well and it's possible the side effects won't be too harsh.  However, chemo and immunotherapy each have side effects that can be harsh and together they are compounded.  She won't know until she tries how she responds.  A couple of notes on side effects.  Nab-pax is noted for the neuropathy it can cause.  Most people with adeno find pemetrexed to have fewer side effects than a taxol and anecdotally pemetrexed seems to have better outcomes.  on chemo immunotherapy

Whatever her plan she can always change course to suit. It's a difficult time trying to balance harm and benefit when so little is sure.  Listen to your mom's nurses, and encourage her to ask the chemo nurses and oncologists' nurses for help or input for managing side effects so to live life a bit.  

I hope some of this is helpful and don't hesitate to ask for clarification or whatever.

Take care,

Janine

Yes, all of the brand-named drugs are different drugs.  Each drug in a generation of drugs is similar in makeup but usually quite different in efficacy and side effect profile.  I'm talking about the FDA (US) and MNPA(China) approved drugs.  Not all countries abide by these patent rules and manufacture generics of these drugs which are sold as being the same thing as the patented drug.

I am not aware of people trying 2 TKIs concurrently.  In any case, the exon 20 TKIs are sequenced after platinum doublet chemo.  The side effects of taking 2 TKIs may be too harsh. 

As I've said before, a consultation with a specialist at an academic center with a specialty in lung cancer and even Targeted therapies along with all of your mom's individual info would be much more helpful at answering this question.  One question I would have is about taking chemo (alimta/carboplatin) without immunotherapy so to leave room for the possibility of taking another TKI such as sunvozertinib if you're in China it was just approved for after platinum chemo.

I hope this is helpful.

All the best to you and your mom,

Janine

Yes and yes. 

T790M is an alteration mutation that occurs at exon 20 and points to resistance to 1st and 2nd generation TKIs fortunately tagrisso works against T790M. 

and

egfr exon 20 insertion is a different issue from t790m.  From onclive and kinda technical, "The novel irreversible EGFR exon 20 insertion inhibitor sunvozertinib (DZD9008) demonstrated significant clinical activity and similar safety to prior reports in Chinesepatients with non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations who progressed on prior platinum-based chemotherapy, according to results from the phase 2 WO-KONH6 study (NCT05712902) presented at the 2023 ASCO Annual Meeting.1" 

I'm wordering what you meant when you said, " she was prescribed Tagrisso for three months. However, the response to this treatment was not as favorable as we had hoped."  I'm now seeing, not as favorable, as there was no progression.  If that's so it was working and may work again.

I'm so sorry wel sun.  If she has exon 20 insertion she may be able to take sunvozertinib after chemo.  I hope she does well on chemo, let us know.  I know how stressful and scary it all is.  Your mom is lucky to have you advocating for her.  Take care of yourself too.

Janine

Unfortunately, there isn't enough known about nsclc with multiple mutations (compound (driver) mutations) to say what treatment is likely best.  Here is a conversation on the subject.

The more drugs in a combination the more each side effects are heightened.  That isn't to say that your mom will have overwhelming side effects but it's something to be aware of.  She can always stop any or all of them. 

If she were to just pick one alimta/carbo or even alimta alone has had good efficacy for those with an egfr mutation.  But yes that combo is being used and studied for efficacy in those with resistance to TKIs.  As the video linked to above suggests there isn't good understanding of what the best options for those with compound driver mutations.  They seem to be a different animal all together. I wish I could give good objective info.

All the best of luck,

Janine

Tagrisso is the latest drug to treat egfr mutations.  Also, taking an egfr targeted treatment after taking immunotherapy causes dangerous lung inflammation in many people. 

I am so sorry that your mom hasn't responded to treatment.  Unfortunately, when someone doesn't respond to this standard of care it's been noted that they are also unlikely to respond to lesser likely drugs. 

When treatment is no longer an option, hospice care can help provide excellent comfort care and are tremendously helpful to family caregivers. 

I wish there was better info I could give.  Best of luck to you and yours,

Janine

Blue Sun, I'm glad your mom found the right treatment and is feeling better.  Yes, it must be the MET mutation that took over.   I hope it lasts a long time and she is able to return to living life.  And thank you so much for returning to GRACE to share your good news with others. 

Take care,

Janine

Hi happybluesun,

I'm glad your mom has done well but hate to hear about the new progression.  There is possibly still efficacy overall and resistance in just the one or 2 or 3 spots that may be controlled with local treatment such as radiation.  Info on oligoprogression can be found here.

I'm not sure that you said which EGFR drug was used so I'll leave you with this in case she's not used the combo (now FDA approved) of Amivantamab and Lazertinib. 

Best if luck to you and your mom,

Janine

I could not find any info on the combination almonertinib and Capmatinib so there is no way to compare it with amivantamab and lazertinib combo.

However, the amivantamab/lazertinib combo has a lot of research behind it and is a proven combination.  It's worth a conversation with your mom's oncologist.  Here is some of the latest info.

Here's a new video on the study (it's the Mariposa study and starts about half way through the vide

From the manufacturer

and from NEJM.

FYI, there usually isn't a problem approving a first line treatment for use in later lines.