Adenocarcinoma with Egfr+ mutation exon 18 & 20

sbunit
Posts:6

My 81 year old mother was recently diagnosed with stage 4 adenocarcinoma with metastasis to her spine along with a malignant pleural effusion (no other organ involvement and negative for brain meta sis). Prior to this she had been suffering from rheumatoid arthritis and was taking Embrel, a biologic, which her physicians suspect may have contributed to the cancer (she never smoked a day in her life). Her mutations on exon 18 and 20 are considered uncommon and between that and her rheumatoid arthritis, made treatment a little tricky as they did not want to try immunotherapy as an initial treatment (she tested 40% positive on PDL). Instead they decided to place her on Tagrisso which she has been taking for the past month with minimal side affects, just more frequent bowel movements and fatigue. We aren’t due for a follow up scan for about another month but I was wondering if anyone has any experience with these mutations and if feedback can be provided

For what it’s worth, I initially thought the exon 20 mutation was an insertion mutation based on Al my internet research and the limited information out there. Turns out that it is not an insertion mutation and instead it’s a substitution mutation on exon 20 which her oncologist seems to think will generate a favorable response from the Tagrisso. Again any insight and general prognosis would be greatly appreciated. My mom is symptom free for the time being aside from the frequent bowel movements and inconsistent fatigue.

JanineT GRACE …
Posts: 606
GRACE Community Outreach Team

Hi sbunit and welcome to Grace.  I'm sorry about your mom and you need to be here looking for answers.  Unfortunately there just aren't good answers to these questions.  But yes there seems to be better activity with EGFR TKIs with substitutions in exon 18 and 20 than in the insertions there.  While it is uncommon to see 2 driver mutations when it happens it's usually with these substitutions at 18 and 20. 

This is a link to a study on the subject.  As a layperson who had to read a bit of studies in school, I did a search/find of "substitution" as well as focused reading results and conclusions. 

 

Chemo usually has good efficacy in people with EGFR mutations.  There are excellent premeds that mitagate a lot or even most side effects, or smaller doses of chemo drugs can be used.  Sometimes radiation to bone mets are used to stablize the bone. 

 

I hope your mom does well on tagrisso for a long time.  Please let us know if you have further questions and keep us posted.

All the best,

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.

sbunit
Posts: 6

As a follow up to my original question, the specific mutations my mom has are S768l and G719S. It’s very difficult finding concrete information regarding these mutations and treatment outcomes. Was wondering if anyone has any experience regarding these mutations and their general prognosis. Mom is currently on Tagrisso 80mg

JanineT GRACE …
Posts: 606
GRACE Community Outreach Team

Hi, I'm sorry that I missed your follow-up question. These subtypes are the ones discussed in the report I linked in my previous post. BTW, I don't think I was very clear when I tried to describe how I read professional study reports. So let me try again. When I was in school I had to read a lot of studies and I read a lot of them when learning about my husband's cancer. They are very difficult to impossible to understand. So what I do now is use my "find" key shortcut, in my browser "Ctrl F" to search for specific words or terms, and I usually skip to the "conclusions" and "results" of the study even if I go on the read other parts of the reports.

 

The reason for holding off of immunotherapy is that using TKIs after immunotherapy has caused a lot of pneumonitis so you want to use up TKI options before moving to immunotherapy.

 

I hope your mother is still doing well.

All the best,

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.

sbunit
Posts: 6

Hi all

This is a follow up to my original post about 15 months ago when my mom was first diagnosed with stage 4 adenocarcinoma. She’s been on Tagrisso since and it has been working well, shrinking her primary tumor without any further evidence o progression. Unfortunately because she’s quite frail, she tends to experience a lot of stomach problems from the Tagrisso. This past September she was experiencing quite a bit of diarrhea, stool samples were negative and her oncologist was suspicious it was related to the Tagrisso so he halved her dose from 80 to 40 (I think these are the correct numbers but I am 100% sure the dosage was halved). She’s been on this half dosage since then, the diarrhea was resolved (her taste has also improved prior to this she was complaining everything she ate tasted bitter) but she still experiences GERD like symptoms and stomach pain (which were her initial symptoms prior to diagnosis!).

Finally to my question:
She just had blood work done and her CEA markers have been on the rise. She is due for her next set of CT scans. Her last scan in October showed everything to be stable with no appreciable changes. We are concerned with the rise in the CEA marker, does this indicate the cancer is growing again? I’ve read that CEA is not a good indicator for lung cancer but I also read other things that say it can be highly associated with egfr related lung tumors which mom has. If the tumor is growing again, can I assume the next step would be to raise the dosage of the Tagrisso again? Any insights are greatly appreciated

JanineT GRACE …
Posts: 606
GRACE Community Outreach Team

Hi sb, it's good to hear your mom is feeling better with the halved dose and your mg numbers are correct. It's a common adjustment when side effects become unmanageable.  You're right that CEA counts are not a good indicator of progression so hopefully there will be nothing to change.

 

If the lower dose isn't sufficient and there is progression upping the dose to its original mg is probably the first option she and you would discuss with her oncologist.

 

If there is only slight progression (you have to squint to see it)  it may not be worth changing anything.

 

Since tagrisso has the smallest side effect profile, generally speaking, changing to a different regimen would likely cause more side effects. So adding chemo is probably out.  The single agent alimta without tagrisso may be an option. It's proven to be helpful for many who are considered too frail for platinum doublet. Immunotherapy hasn't proven to be a good option for egfr+. 

 

Have you seen our most recent webinar forum on targeted therapies?  here's a list of shorts from that forum. https://youtube.com/playlist?list=PLWsyUmdjLXhFX9EGwlx96S-cez41zU57z&si=SWFtz13RHHOKpnQ3

 

Thank you for returning with an update.  These conversations can be invaluable to others.

 

Hoping for no changes.

All the best,

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.

sbunit
Posts: 6

Janine thank you so much for the reply

Based on my mom’s recent symptoms (which after speaking to her today mimics all her symptoms prior to initial diagnosis last summer), and the fact her Tagrisso dose was halved about 4 months ago, I am highly suspicious and expecting to hear that her tumor has grown again once she gets her next scan (trying to get scheduled for this week). I was wondering,

1) is it common to see the tumor/disease progress after halving the dose of Tagrisso?
2) is the likelihood of the tumor/disease getting back under control high/good once you increase the dosage of Tagrisso again which is what I’m assuming will be suggested

Basically, is this a commonly seen scenario where the dose is lowered and the disease decides to progress but can be brought under control again later by increasing the dosage? Just worried about what the future may be holding and hoping there may be an easy fix to this. 15 months on Tagrisso (with the last 4 months only at half dosage) hopefully doesn’t mean it stopped working

JanineT GRACE …
Posts: 606
GRACE Community Outreach Team

Hey sb,

I don't think there's specific data on the likelihood that moving back to full dose will bring the cancer back under control but it is done and with all things being equal I'd think there's a good chance. Often treatment breaks are needed to rest the body and mind.  I know how important it is for you to have expectations of what's going to happen next but the truth is anything is possible which makes planning a step or 2 ahead a never ending process.   

 

Have you spoken with her oncology team about these things (new old symptoms, scans, followup appointment, possibly moving back to full dose)?  That's important so they understand how immediate any changes need to be.

 

Your mom is very lucky to have you in her corner.  Please keep us posted.

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.

sbunit
Posts: 6

As always, thank you so much Janine for your responses.

While we are awaiting her scan, the other question I have is regarding her chronic pleural effusion. At her initial diagnosis mom had malignant pleural effusion. As stated she was placed on Tagrisso (initially 80mg) since then with no other form of treatment and it seems to be working well (pending results of her upcoming scan of course). At her last Ct scan back in Sept 2023, The pleural effusion was still present with adjacent partial atelectasis (also present at initial diagnosis in August 2022) without significant interval change compared to prior scans. While I suppose the no change is great, I was wondering if it is common/typical for a chronic pleural effusion to still be present 15 months after initial diagnosis and treatment? The effusion did get smaller compared to the original size but it has never disappeared entirely. Mom has not had any symptoms until these past 4 weeks where she is suddenly experiencing primarily GI related symptoms (stomach pain, occasional vomiting of a yellow substance possibly bile) in addition to body chills at night and lower extremity pain. Hoping the cancer is not getting out of control and perhaps something else may be going on.

She is being scheduled for her CT scan and I will certainly be discussing matters further with her oncologist once we receive the scan results.

JanineT GRACE …
Posts: 606
GRACE Community Outreach Team

These new symptoms need to be discussed with her oncology team (oncologist's nurse is usually the go-between in matters like that) now over the phone or however you communicate with them and not wait until her appointment after the scan. 

 

The rule of thumb is to report and get a response about any new or worsening symptoms...anytime. They may want to put her back on full dose or manage the new symptoms.  That's something she hasn't needed to do so I understand this is a new type of situation but this is an important and clear standard of care. 

 

Keep us posted and 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.

sbunit
Posts: 6

As an update to my previous post, we took mom today to her pulmonologist to see what we can do about her symptoms as we continue to wait for the insurance company to authorize her chest CT. Mom has been having worsening GI symptoms. An ultrasound was taken this morning and as suspected her pleural effusion has gotten bigger (She had the same symptoms prior to initial diagnosis of her cancer). She is scheduled to be drained in the next 48 hours which should alleviate her symptoms and discomfort. I didn't have a chance to discuss anything with her oncologist yet but of course I asked her Pulmonologist if this means her disease has progressed to which he responded yes likely.

As mentioned, her Tagrisso dosage was cut in half back in September (4 months ago) when she experienced 2 weeks of diarrhea without cessation. She's been on 40mg of Tagrisso since then. He told me the question now becomes, did the disease progress because of the lower dose or because the Tagrisso has stopped working entirely (I.e. resistance). He did not know the answer to this question but he will be reaching out to our Oncologist to inform her of today's findings. Do you know what happens next? If it stopped working, what options do we have? Mom has substitution mutations on exon 18 and exon 20. Is chemo going to be inevitable? Mom is very frail, only weighing 90lbs and i am very fearful she would not tolerate the Chemo. Again, thank you so much for your generosity with your time to answer my questions.

JanineT GRACE …
Posts: 606
GRACE Community Outreach Team

Hey,

 I'm sure you're relieved to see progress in her clinical care. Without actually trying, it's uncertain whether returning to the full dose would be effective or if Tagrisso has lost its efficacy. If your mom and her oncologist deem her fit enough, they might consider trying single-agent Alimta, which has shown benefits for frail individuals. I recognize the difficulty in broaching the subject of transitioning from anti-cancer treatment to only comfort care, as it signifies the end of life (incidentally, moving to hospice care before the dying process begins normally lengthens both quality and length of life.  Timing is crucial to ensure your mom's and your comfort, and hospice care professionals are highly skilled in addressing individual needs. It's vital to maintain an open dialogue, signaling to her treatment team that discussions about discontinuing anti-cancer treatment in favor of comfort care are welcome and not to be avoided.  I'm not suggesting it's time your mom stops treatment I'm suggesting it's time for it to be an option that is discussed.  Unfortunately, in the US we don't normally transition to hospice soon enough and miss out on the opportunity for some excellent quality time with loved ones. 

With all that said, I hope tagrisso still has efficacy for your mom.  As always, take care and please keep us posted,

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.