Multiple EGFR mutation lung cancer

happybluesun
Posts:7
n/a
Dear GRACE, In 2020, my mom was diagnosed with right lung adenocarcinoma, which led to her undergoing surgery. Unfortunately, the cancer had spread to her left lung by 2021, requiring another surgery followed by four cycles of chemotherapy. Both instances of the cancer were identified as having the EGFR exon 21 L858R mutation. In April 2022, a new development occurred as the cancer metastasized to her right clavicular lymph node. To address this, she was prescribed Tagrisso for three months. However, the response to this treatment was not as favorable as we had hoped. As a result, radiotherapy was pursued, yielding a positive effect. As of June 2023, a PET/CT scan revealed an unsettling progression of the disease. Multiple lymph node metastases were detected in various regions, including bilateral clavicles, mediastinum, both lung hilums, behind the diaphragmatic foot, abdominal cavity, and retroperitoneum. Genetic testing uncovered the presence of several EGFR mutations (exon 21, exon 20) within the EGFR gene, along with a TP53 mutation. Given the complexity of these multiple EGFR mutations, I have reservations about the potential efficacy of further targeted therapy. I am reaching out to seek your insights on the recommended course of treatment at this juncture. Additionally, I am curious if you are aware of any other patients who have encountered similar cases and what approaches have been explored in those instances. Your guidance and support would mean a lot to us during this challenging time. Thank you for your attention and assistance
wei sun

JanineT GRACE …
Posts: 628
GRACE Community Outreach Team

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

I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

happybluesun
Posts: 7
n/a
Hi Janine, thank you very much for your reply. As of June 2023, my mom has been prescribed Almonertibi Mesilate Tablet, a targeted therapy medicine made by the Chinese company Haosen Pharmaceutical because her cancer has spread to various regions. The recent report shows no obvious results from this treatment, plus my mom has experienced serious side effects. The doctor told her to stop the current medication and switch to immunotherapy RIGHT WAY. The immunotherapy formula is TECENTRIQ® (atezolizumab)+ Bevacizumab+ Albumin-bound Paclitaxel (Nab-paclitaxel) +Carboplatin. I was informed by a prominent US doctor that immunotherapy and targeted therapy drugs should not be used concurrently. There should be a few months' gap to allow the targeted therapy drugs to clear from the bloodstream; otherwise, there could be life-threatening side effects. I have told my mom not to start the immunotherapy formula until I receive confirmation from the U.S. side. In China, the formula TECENTRIQ® (atezolizumab) + Bevacizumab + Albumin-bound Paclitaxel (Nab-paclitaxel) + Carboplatin seems to be a last resort, used when all other methods have been tried. Unfortunately, most patients experience very serious side effects. A friend's mom received this treatment for two months and her health destroyed significantly. I am deeply concerned about this new treatment plan, and your guidance and support would be greatly appreciated. Thank you very much!!

wei sun

JanineT GRACE …
Posts: 628
GRACE Community Outreach Team

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

I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

happybluesun
Posts: 7
n/a
I agree with you that we should explore all possible TKI options before switching to another one. When you mention 'TKI options,' are you referring to various brands produced by different companies? Additionally, can different targeted therapies for exon 20 and exon 19 & 21 be taken concurrently? Thank you very much for your reply!

wei sun

JanineT GRACE …
Posts: 628
GRACE Community Outreach Team

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

I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

happybluesun
Posts: 7
n/a
For knowledge purpose, I find myself puzzled by the distinction between the exon 20 T790M mutation and the exon 20 insertion mutation. Am I correct in assuming that they are distinct from each other? Is Sunvozertinib effective exclusively against the exon 20 insertion mutation? Thank you very much.

wei sun

JanineT GRACE …
Posts: 628
GRACE Community Outreach Team

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 joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

happybluesun
Posts: 7
n/a
The tumor was spread to Right clavicular lymph node in April 2022. So she was prescribed with Tagrisso. But the tumor continued to grow despite the intake of Tagrisso. It is so weird. It seems targeted therapy just does not work for my mom. :(

wei sun

JanineT GRACE …
Posts: 628
GRACE Community Outreach Team

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

I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

happybluesun
Posts: 7
n/a
My mom is going to try the chemo and immunotherapy treatment. Targeted therapy is not working on her. Just to double confirm with you about the recipe of chemo and immunotherapy. Is it TECENTRIQ® (atezolizumab)+ Bevacizumab+ pemetrexed +Carboplatin? My mom is not in good health right now. She coughed a lot from the targeted therapy. I just want to find the combination with least known side effects for her if it is possible. Thank you very much for your kindness in replying my message.

wei sun

JanineT GRACE …
Posts: 628
GRACE Community Outreach Team

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

I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

happybluesun
Posts: 7
n/a

I've heard that the 4th generation of EGFR inhibitors can overcome EGFR resistance. Do you have any information about that? Do you know any way we can get some of the medicine? My mom is nearing the end of her life, and I am trying to see if I can find any of the 4th generation inhibitors to buy her some more time in this world. Thank you very much for your help.

wei sun

JanineT GRACE …
Posts: 628
GRACE Community Outreach Team

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

I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.