Progression on Tagrisso (Osimertinib)

zhengchenji18
Posts:30

My father have been on Tagrisso for 5 years since 2015 with no progression until recently. Below is the new CT report in July comparing the CT in Jan 2020.

He did have EGFR with T790M positive. Tagrisso is the second-line treatment with Iressa as the first-line. My father does not have any symptoms at the moment.

We live in Toronto with the possibility of clinical trials. Will be seeing our oncologist this Thursday.

Would love to get your thoughts on the following question:

1. Unfortunately, there are some signs of progression with the two bone mets.

Are these mild progression? I have listened to many videos on this wonderful site. Perhaps we can wait for another CT scan in 3 months? Or maybe 3 months is too long to wait

In the meantime, is it reasonable to try Radiation therapy to the two bone mets?

2. In this video below, Repeat Biopsy seems like a good idea.

I am wondering if it is possible to take biopsy to the bone now given the size.

https://www.youtube.com/watch?v=JhqUABGdPYY&list=PLWsyUmdjLXhHekSOlZGFTl7kb8pmKQ9BL&index=22&t=0s

3. The current CT covers the upper body. Do you think it would be reasonable to check if there are any brain mets or CT for the lower body?

My grandma had lung cancer and brain mets.

Many many thanks!

CT: Edit the post

1.2 cm , prior 1 cm lesion in the bone

1.3 cm , previously 0.8 cm lesion in the bone

conclusion mild progression

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi zhengchenji,

 

Welcome to Grace.  I'm sorry your father is going through this.  Though it's good to know that he's been doing well for so long on a pill, no less.  Another upshot of that is responders tend to respond to other treatments.  Next time it's not a good idea for privacy to post CT report.

 

Your father has one spot of "slight" progression, also known as oligoprogression.  The 2mm difference in the other lesion may just be a difference in the cut of the previous CT so maybe watch and wait on that one.    1 or 2 or maybe 3 spots are normally handled with radiation and continue on with tagrisso as before.  Some people take a break from tagrisso during radiation some not. 

 

A biopsy would be done to decide on treatment after tagrisso no longer manages the bulk of cancer.  Hopefully, whatever a biopsy would find right now will be gone after radiation.  It sounds like your father is doing really well with tagrisso!  A chest CT every 9 or 12 weeks is average, there's no standard on timing.  As long as your dad doesn't have symptoms of brain mets there's probably no reason for brain mri.  

 

I'm sorry about your grandma.  Current thought is there must be an inherited gene mutation that combines with other causes that cause types of nsclc.  This link's to a quick look at what we know we don't know about inherited gene changes from cancer.org.   I don't know but I'd think something like a once a year low dose ct might be appropriate for screening.  Whether to screen or not to screen there's surely a standard in your type of situation. 

 

Keep us posted and 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.

zhengchenji18
Posts: 30

Appreciate your comment and i removed the CT results as you suggested.

One more question, I read on a few articles that EGFR+ patient tends to repond poorly to chemo. 

Just wondering if you have the same view, a bit worried that chemo is likely the next line of treatment.

Will update when we see the doctor on Thursday!

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

In the first minute of this video as Dr. West introduces the topic of concurrent vs. sequential tki and chemo he states that chemo has a substantial overall survival benefit.  Perhaps the statements you've read and heard of are comparing the efficacy of the tki vs chemo and yes the tki generally speaking, has longer PFS than chemo.  I'm speaking of statements oncologists have made that their patients with an EFGR mutation seem to do better on chemo than other nsclc patients.  It's been an observation, not a data-driven fact.  I can't find that statement anywhere since it's been an off-hand observation and not the topic of discussion.  Let me check with Dr. West and make sure I'm not making this up. 

 

How did the appointment go? 

 

Stay safe,

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.

Dr West
Posts: 4735

I would say that progression of a couple of bone lesions is widely considered to be "oligo-progression" that may be addressed with radiation and remaining on Tagrisso (osimertinib) -- though that isn't a universal plan.  Also, measuring the size of bone lesions is notoriously difficult and unreliable -- in fact, bone lesions aren't even considered as "measurable disease" in clinical trials.

It would also be reasonable to try to biopsy an area of progression, but these are still small lesions, and it tends to be harder to get molecular testing results from bone biopsies because you need to do a chemical treatment to remove calcium from the bone, which can degrade the genetic material. Also, it's worth noting that using a repeat biopsy after progression on Tagrisso is not a standard of care and isn't something I would say is high yield, even if it's something that is often tried, especially at cancer centers doing research.

EGFR mutation-positive NSCLC definitely responds to chemo, and there have even been occasional studies that indicated that patients with EGFR mutation-positive cancer respond better to chemo than EGFR mutation-negative cancer.  That hasn't been a universal finding, and overall I would say that these days we would be inclined to consider EGFR mutation-positive NSCLC to respond at similar levels as a broader population. I think any interpretation that patients with EGFR mutation-positive NSCLC don't respond well to standard chemotherapy would be misinterpreting -- these patients do have higher response rates to EGFR inhibitors, but that's because the EGFR inhibitors work especially well in these patients, not that chemo works particularly poorly.

I hope that helps.

-Dr. West

zhengchenji18
Posts: 30

First of all, thanks to Dr west and Jannie for the quick and thorough response. I really appreciate it.

Update from Thursday,our doctor decided to wait 3 months and see the new scan results.

continue taking Targrriso

we asked about

1. Biopsy: doctor said no, maybe later

2.Radiation: doctor said no, until my dad shows symptoms she would consider 

3. Brain MRI: doctor said no because no headaches, losing eye sight etc

I think these are all reasonable responses. The only concern is that our Dr seems to be less enthusiastic on clinical trials for my Dad. If I interpret Dr West correctly, he seems to think there aren't any clinical trails that is really "high yield" in my Dad's case. So I guess both doctor thinks alike. 

I will update again in 3 months in case this content is beneficial to others.

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

The 3 months wait and see sounds like a good plan.  Even when the spine met grows and causes problems he would still remain on tagrisso since it's just one or two places that would need radiation treatment.  Encourage your dad to let his onc know of any new pain in his back asap because you want to address the spine mets before they cause damage that is either difficult or impossible to manage.  

 

I don't believe Dr. West was suggesting a clinical trial won't be appropriate.  He was just saying that bone mets are difficult to biopsy and difficult to analyze so aren't considered appropriate to use for admitting someone into a trial (I suppose unless the trial is specifically about bone mets.)

 

As a matter of fact, clinical trials for those with 1) an egfr mutation, 2) acquired resistance to tagrisso, and 3) presenting a new mutation are relatively plentiful.  That's because there are many drugs being tested on the plethora of mutations that have recently been found.  The take-home today is your father isn't done with tagrisso, even when the met on the spine needs treatment. 

 

All things considered, this is pretty good news. 

Be safe,

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.

Jim C GRACE Co…
Posts: 147

GRACE Community Outreach Team

Hi zhengchenji,

 

Just a couple things I would add to the previous responses. Measuring the change in size of bone mets doesn't tend to be used in clinical trials because they are so difficult to measure that it becomes difficult to judge whether the trial drug has been effective. That doesn't help the trial investigators assess the efficacy of the drug. In light of that, and since the progression is only in the bone, with Tagrisso otherwise seeming to be keeping the cancer under control, it may be premature to consider a trial. Add to that the fact that your father has not been treated with chemotherapy, which is often the next step if an EGFR inhibitor becomes ineffective, and your doctor's suggestion to wait and see seems quite reasonable.

 

I hope that your father will be able to successfully continue with Tagrisso, and that if necessary the bone mets can be controlled with radiation.

 

Jim C Forum Moderator

 

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

 : ) And that's why 2 heads are better than 1 and 3 better than 2.  Thanks Jim for chiming in.  You always provide helpful perspectives.

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.

zhengchenji18
Posts: 30

Thanks for your help in advance, would be great if we could get some insight by Wednesday before our doctor visit.

New CT results came out with two findings

1. The bone lesion mentioned in the last CT report in July 2020 has grown to 1.7cm from 1.3cm

 This is compared to 0.8 cm from the CT report on Jan 2020

2. "Soft tissue density around the bronchial stump appears slightly more concave" 

22 x 11 mm, previously 18 x 8 mm in July 2020. 2 years ago 15 x 5 mm

Can you please help me interpret how concerned about the growth rate?

The bone lesion appears to grow at a constant 0.5cm every 6 months. I thought the rate should be accelerating.

My dad is feeling pain in the bone now, although it is not very serious(not taking pain killer).

What is the best course of action?

Tools available: 

Continue taking Osimertinib

1. Radiotheorpy of the lung and bone

2. bio marker testing (C797S, BRAF etc)

2a. for C797S, can my dad go back taking Iressa? Heard that we can retry Tarceva if C797S have been detected(We are in Canada)

2b. for bio marker testing, should we go for tissue testing from bone or blood test?

3. Maybe adding Avastin? I heard that it might slow down progression.

Chemo

Is it too early to go for Chemo now since my Dad only two identifiable lesions?

Has there been any new development in ASCO 2020?

 

Thanks a ton!!!!!

Happy new year,

Chen

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Chen,

 

Happy New Year to you too.  I'm glad your dad is still doing pretty well on tagrisso.  As far as his cancer growing faster it's a matter of his treatment and his individual cancer.  As most oncologists are known to say, cancer can and will do anything.  You really shouldn't assume too much about the future of his journey at this point.  You're being an excellent caregiver by staying on top of next options.   The best course of action can only be made by your dad, his oncologist, and probably at least in part by you too.  Your dad's oncologist can review the whole picture and with your knowledge, your dad's wishes, the best course of action can be made.  But you have listed the possible next steps. 

 

We can't interpret your dad's scans, again it takes having the whole picture to understand what it means plus it would be unethical and illegal. 

The growth seems slow which is most likely due to tagrisso.  In a case where tagrisso is being used and there is growth of up to 3 or even 5 sites radiation is considered with continued use of tagrisso.  Since your dad is beginning to experience pain with the bone met it's quite possible that radiation can stop the progression and decrease the pain.  The pain in all likelihood will continue to worsen without intervention.  Biopsy of bone is difficult to get, it's painful, it's complicated and time-consuming to break down and isolate the cancer, and very often you don't get enough actual cancer cells to use in testing. So biopsy of bone is a last resort situation.

 

All in all, it sounds like your dad is in a decent situation.   I'll post a recent video on the subject in a few. 

 

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.

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

video on liquid biopsy (blood biopsy)

sindas trial  round table discussion  This trial looked at 1st line treatment but the conversation in this round table discussion is relevant. 

 

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.

zhengchenji18
Posts: 30

Thanks again for all the help!

I want to provide some update from our latest doctor meeting.

1. We can stay on Tagrisso

2. The met in the bond will likely be radiated, booked a meeting with radiation oncologist

3. We are provided the opportunity to go on the JNJ-61186372 Phase I trial. A blood sample was taken to conduct molecular testing for C797s mutation.

We think the direction is correct and happy with how the meeting went.

I am just wondering if you have any more information on this trial given it's only a phase 1 trial.

Also, is there any paper mentioning the accuracy of the blood mutation testing?

Thanks,

Chen

 

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Chen,

 

It sounds like your dad's on a good path.  Oncologists like to stay on a treatment for as long as they can before moving on and tagrisso has been a very mild anticancer drug for most people and many have stayed on the drug for years.  If a treatment is causing unmanageable side effects it makes sense to discuss moving on; there are no guarantees that going back to a treatment will work as it did before.  But a phase 1 trial testing safety doesn't have data to suggests stopping a working treatment that's a pill, you don't have to leave your home to take, that isn't causing unmanageable side effects, and is keeping metastatic nsclc in check.  I don't know of a good reason to leave a working treatment for a maybe.

 

I'll look around for more info on mutation testing.  The accuracy seems to depend in part on the amount of mutation dna/rna shedded into the blood.  For those with nsclc limited to the lungs there is often not enough dna to capture in blood biopsy.  I imagine you have but have you listened to the video linked in the post just above your last post?

 

I hope your dad and you are doing well,

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.

zhengchenji18
Posts: 30

New updates on the situation.

The sequence of events:
Being on AZD9291 or Tagrisso, we are located in Toronto Canada
Jan 2021- one tumor in the right lung is found to be growing from about 1.5cm to 2cm
July 2021 - tumor continues to grow to 2.5cm, although no major symptoms
Sep 2021 - radiation performed against tumor
Nov 2021 - tumor shrink by about 20%
Jan 20 2022 - CT scan shows everything stable
Mar 05 2022 - Dad went to the emergency department for severe abdominal pain
Ultrasound and CT were performed
Doctors was not able to find anything new in the abdominal area
However, they found mild to moderate pleural effusion on the right side and a lymph node measuring 1.6x1.3cm.
Dad said feeling some discomfort in the right lung but no other pains for 3 days.

We don't want to switch off from the targeted drug since it has been working so well.
However, since he was doing well in the CT in Jan 2022, the recent development in the last month is concerning.
Should we wait and see another two months or seriously consider switching to chemo?

Also, I am guessing the first order of action is to drain fluid if there are enough?
This can be tested to see if there are cancer cells.
We are also not sure if pleural effusion can cause abdominal pain (kinda strange).

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Chen

I'm sorry your dad is having new pain. It very possible the pain is from the PE, his onc should probably be able to glean that during the check up today.
Stopping tagrisso probably isn't going to be on the table for now. It's more likely to stay on tagrisso because it's mostly keeping the cancer under control. Often local treatment is used to stop a small outbreak of resistance.

I hope the appointment is helpful in getting the abdominal pain straightened out and the PE under control.

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.

zhengchenji18
Posts: 30

Thanks, seems like the pain has gone away for now.

An additional new scan just occurred this past week, it's showing that he has an enlarged heart.
I know Tagrisso can lead to an enlarged heart from the document link below.
However, he has been on Tagrisso for almost 5 years without this issue.
Question: Is it likely the cause of enlarged heart is something unrelated to cancer/Targrisso?

https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformati…

Carol2022
Posts: 1

Hi Chen,

I am in USA. My father just started taking Tagrisso 2 weeks ago (EGFR ex19 Del). The below is the result of PT-CT scan from this March:
Chest: FDG avid right pulmonary mass within the right lung on axial image 98 series 3 measures 5.1X3.5cm (best visualized on fused axial image 100) with maximum SUV 7.9/ It is difficult to appreciate which lobe of the lung this mass is within, secondary to extensive surrounding collaterals.
A few prominent minimally avid lymph nodes are present within the mediastinum. For instance:
Subcarinal lymph node on axial image 84 series 3 measures 1.2X1.0 cm with maximum SUV2.4.
Precarinal lymph node on axial image 77 series measures 1.2X0.9 cm with maximum SUV 2.2.

My father is now suffering shortness of breath and losing appetite. He already lost 20 lb weight since March. Is there any way to help my father eat more and gain weight? Any suggestion is much appreciated!
Chen, we can contact via wechat (mine ID is starmellow) if possible.
Thank you and have a great day!
Carol

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Chen, I'm sorry your dad has this new issue. We can't say what caused the enlarged heart but it could be tagrisso even this far from starting. But as you've suspected it could be unrelated. Here is a good description of an enlarged heart including causes and treatment. Stopping tagrisso is probably on the table since eliminating the cause is the best treatment. 

 

If he is able to begin chemo and/or immunotherapy are options. 

I'm glad the pain is better and I hate his heart is suffering.  Cancer is terrible.

 

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.

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Carol,

 

It usually takes between 6 and 12 weeks for tagrisso to begin working.  If it does benefit your dad it could eliminate the issues you've described. 

 

Here is an article on shortness of breath.  You can scroll down to treatment since you've got a good idea of what and why.  As you'll see the first 3 options are all "Treat the underlying cause" which he's doing.  There are several other treatment options to get him comfortable until tagrisso begins to help. 

 

This is a good list of things to try.  I didn't see these things mentioned, magace (if it's appropriate since it's got it's own side effects) though not very effective when the cancer burden is high.  My husband drank lots of ensure plus and ate lots of mashed potatoes with butter and cream chz.  Taste often changes so if he's not interested in normal favs try something other. 

 

I'm leaving you with lots of info in those 2 links.  They are an important package of tips for caregivers and hope they will be helpful to you and I hope your father recovers from these symptoms with tagrisso.  Keep us posted as there are too many people looking for this type of info.  I'm curious if this is his first line of treatment.

 

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.

Rowan
Posts: 18

Hello, i did not expect to be back here so soon. My mother was given tagrisso in nov 2020 for stage 4 nsclc. She initially had a brain met which was treated with srt.

After her routine pet scan in early may 2022 there was progression with a new deposit and one supraclavicular lymph node. The deposit was removed by surgery on may 19th. Lymph node was not, it was away from the deposit and the doctor wants to test the deposit.

What is the latest approach to dealing with progression on tagrisso? Her initial biopsy showed high pdl-1 but back then keytruda was not given for egfr patients. Since then i have read testimonies from some patients who have received immunotherapy after tagrisso. She will be doing NGS biopsy and brain mri soon. I am scared she wont have options left. I did not expect her to progress so soon on tagrisso.

Kind regards

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Rowan,  I'm sorry you're back too. If there were such a thing as best of both worlds in lung cancer it would be having an egfr mutation that responds to tagrisso and a high PD L1. Normally people don't have both. 

Oncologists want to use a treatment for as long as possible before moving on to another treatment. When there is progression on tagrisso in just 1 or 3ish places, it suggests resistance is limited and can often be stopped with focal treatment such as radiation or surgery. Tagrisso is continued and there is no need for testing at that point. Is there something about the lymph node that makes this an issue for her oncologist?  This short video discusses what is now known as oligoprogression which means progressing in just one or so places. 

 

There may be trial options available that require NGS. Again you want to make sure you get everything out of tagrisso before moving on.

 

When your mom has exhausted TKIs is the best time to move to immunotherapy, not before.  It's become obvious that moving from immunotherapy to TKI too often causes dangerous lung inflammation.  So covering possible trial options of TKIs is important to do before using immunotherapy.

 

I hope your mom isn't done with tagrisso. 

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.

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

I just received this response from Dr. West after describing your post,

 

"I would say that the majority of experts and general oncologists alike would favor using local therapy, most commonly focal radiation for an isolated node or lung nodule that is growing against a background of stability (or shrinkage). You could possibly do NGS, but it's worth noting that it's not standard of care to do repeat biopsies for NGS today, because there is no proven benefit at this time. It's possible that this will lead to a result that could identify a clinical trial or other option, but that is not an expectation today. The strongest clear value of a repeat biopsy in the setting of acquired resistance to an EGFR inhibitor is to identify transformation to small cell lung cancer, which is far more likely to occur when there is extensive progression, both in number of areas and amount of progression. A single area of very slight progression is very unlikely to represent transformation to small cell lung cancer. The other reason not to necessarily do a biopsy is that it's pretty dubious that you'd want to change systemic therapy for mild progression of one site; that's a situation in which we'd really be inclined to continue ongoing systemic therapy with just local therapy (again, likely radiation but possibly surgery) to address to "oligo-progression". Also, PD-L1 doesn't have the same predictive utility in patients with EGFR mutation-positive NSCLC as it does in patients without a driver mutation. It really shouldn't be trusted."

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.

zhengchenji18
Posts: 30

Good morning,

An update on my father who is 67 years old EGFR exon 19 deletion with T790m mutation.
Things have turned for the worse after 8 years on Targrisso.
Last week my dad have one episode of coughing up fresh blood.
He had to ER to get stop the bleeding.
Afterward, it was determined from CT that the main cause is the tumor measuring 2.5x4.2cm.
This tumor was last measured to be 2.1x3.6cm in July.
Some small nodules else where in his right lung but very mild < 1cm.

Three results after seeing the oncologist:
1. Radiation to the large tumor to prevent the future possibility of bleeding
2. It's time to switch next line of treatment, likely chemo
3. Prior to chemo, a new biopsy is to be collected to see if he qualifies for savolitinib.
This drug treats high levels of MET overexpression and/or amplification
https://www.astrazeneca.com/media-centre/press-releases/2022/tagrisso-p…

I have a few questions if you could share your opinion
1. When my father first progressed on Targrisso about 1.5 years ago, he had a biopsy to test for c-met for an antibody drug.
He was denied the trial as there was there was no evidence of c-MET.
Could the gene have changed during the 1.5 years so that he has MET overexpression/amplification now?

2. On switching treatment, the oncologist cites the following evidence as signs the cancer is adding additional burden to his body. Even though it seems quite convincing, I am still wondering if there is any value in staying on Targrisso?
-My father has lost weight from 80kg to 70kg since 6 months ago. His weight hasn't changed much previously.
-My father also reported shortness of breath, likely related to the enlarged tumor near occluding his primary bronchus.
3. Is there any benefit of taking Targrisso along with chemo? Or potentially retake Targrisso after he progresses on chemo?
4. His last mutation result from 1.5 years ago shows PD-L1 @ 60%.
I understand people with EGFR mutation tend to be poor candidates for immunotherapy.
But since he is moving to the next line of treatment, is there any value to try immunotherapy now or save for later?

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Chen, I'm sorry to hear about your father's progression.  I'll try to comment on all your points. 

 

If radiation treatment is effective should he not continue on tagrisso for 12 weeks to see if that solves the problem of resistance? 

Biopsy is tested now before deciding next treatments.  A biopsy from a blood draw may be all that's needed, depending on what is found in the blood tested.  Next-generation sequencing would be the test of choice for a tissue biopsy.

Something has changed since his last biopsy, you want to know what that is so to know the best next treatment.

As it stands today adding chemo to tagrisso is appropriate, that way tagrisso can continue to work on nonresistant cells while chemo works of the other. 

I said, "as of today" because today ESMO (one of the 2 largest cancer conferences of the year is in session with quite a bit being covered in NSCLC.  It is best to check with a specialist in the field of study of the particular genetic makeup studying advanced nsclc...or as close to that as possible.  BTW, have I linked this article here before?, An Insider's Guide to the Second Opinion 

I think the question remains about whether ICI/immunothrapy is appropriate for those with acquired resistance to TKIs.  Certainly, if given it should be after all TKIs.

Here is a link that may be helpful, Resistance on Targeted Therapy: Questions Patients Should Ask-Targeted Therapies in Lung Cancer 2023 and for a long list of topics in the same online forum.  And the whole shabang here and very long...at 2 hr and 24 mins the discussion on only egfr mutations begin. 

 

I hope this is helpful 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.

zhengchenji18
Posts: 30

updates:
My father received standard platinum doublet chemo after Tagrisso.
He progressed on maintenance chemo after a total of 4 months.

The doctor ordered a biopsy of the liver lesion.
Surprisingly, the pathology report indicates that the sample is large cell neuroendocrine carcinoma(LCNC). This is completely different from his original EGFR T790m NSCLC.

Questions:
1. Is it possible that LCNC does not originate from the lung?
2. His PDL1 is > 70% based on the liver sample staining. Is he a good candidate for pembrolizumab even though he has EGFR?
3. what other options does he have?

thanks

zhengchenji18
Posts: 30

The chemo my father received was carbo + pemetrexed.
The standard of care for large cell neuroendocrine carcinoma is actually carbo +etoposide.
Is it worthwhile to try etoposide at this time?

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Zhengchenji,

 

I'm sorry your father has progressed on chemo.  It's more than likely the new tumor is from the lung.  As you probably know it's not uncommon for cancers on targeted therapies to change into other cancers and large cell neuroendocrine is one of those cancers.  Plus, a new large cell NE cancer wouldn't have started in the liver but lung cancer would metastasize there.  Either way it's a rare cancer and not enough is known about it to say what the next treatment should be.  Everything else I say applies only to large cell NE cancer and not any other cancer.  When you start combining treatments to tackle all the variables know that side effects can get overwhelming. 

 

Etoposide may be an appropriate step.  Immunotherapy hasn't been studied well but that's because this is a rare cancer and most everything we know about treatment is from retrospective views.  But yes immunotherapy would likely be an option as well...As long as he has exhausted all TKI options. 

 

With that said there may be TKI options:

It appears that large cell NE cancer can harbor a BRAF mutation.  The following excerpt is from behind a paywall so there's no link and questions about the content would be good discussion points with your father's onc. 

"BRAF V600E mutation — For patients with NSCLC with BRAF V600E mutations, combinations of BRAF and MEK inhibitors are effective; two combinations, dabrafenib plus trametinib and encorafenib plus binimetinib, are approved by the FDA [111,112]. We suggest the use of either of these agents in the front-line setting for such patients, rather than immunotherapy and/or chemotherapy, given the response rates and PFS observed in small phase II studies.

As in melanoma, combination therapy may be more durable than single-agent treatment. (See "Systemic treatment of metastatic melanoma with BRAF and other molecular alterations", section on 'Dabrafenib plus trametinib'.)

Although BRAF inhibition with single oral small-molecule TKIs (eg, vemurafenib, dabrafenib) initially appeared to be an effective strategy in the treatment of progressive BRAF V600-mutant NSCLC [113,114], subsequent trials demonstrated that combination therapy consisting of BRAF and MEK inhibitors is the preferred treatment strategy:

In a phase II study of 57 patients with previously treated, advanced NSCLC with the BRAF V600E mutation, the combination of dabrafenib plus trametinib was associated with an ORR of 68 percent in 52 evaluable patients, and the disease control rate was 81 percent [115]. The median PFS was 10.2 months. The side effect profile was consistent with that observed in dabrafenib plus trametinib clinical trials in patients with melanoma. (See "Systemic treatment of metastatic melanoma with BRAF and other molecular alterations", section on 'BRAF V600 mutant disease'.)

 

In another cohort of the same phase II study, 36 previously untreated patients with advanced NSCLC and a BRAF V600E mutation were treated with dabrafenib plus trametinib [115]. The radiographic overall response rate was 64 percent and included two patients with a complete response and 21 with a partial response. The median PFS was 10.8 months as assessed by investigators.

 

The combination of encorafenib plus binimetinib has also demonstrated promising results in patients with BRAF V600E mutant metastatic NSCLC. In a single-arm study, among 98 patients with BRAF V600E mutant metastatic NSCLC (59 treatment-naïve and 39 previously treated, none with prior BRAF/MEK inhibitors), ORR was 75 percent in treatment-naïve and 46 percent in previously treated patients [116]. The median PFS was not estimable at a median follow up of 18 months in treatment-naïve patients; median PFS was 9.3 months in those with previous treatment. Treatment-related serious adverse events occurred in 14 percent, with the most common being colitis (3 percent).

 

BRAF non-V600E mutations — We do not generally recommend the use of BRAF or MEK inhibitors for non-V600E BRAF-mutant NSCLC.

Other strategies for patients whose cancers harbor BRAF mutations include the use of downstream MEK TKIs as monotherapy (figure 2). While this is of particular interest for some BRAF class II non-V600E tumors that generally appear insensitive to BRAF inhibitors, class III non-V600E BRAF mutations are kinase dead and would not be expected to respond to BRAF or MEK inhibition. (See "Systemic treatment of metastatic melanoma with BRAF and other molecular alterations".)"

 

All the best to you and your father,

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.

rukenk
Posts: 10

Hello everyone, I am here unfortunately after 4 years once again. My mother had been diagnosed with Non-small-cell lung carcinoma (NSCLC) at October 2020 with EGFR and L858R mutation. She had her one lung removed in November and unfortunately, 1 month ago she was diagnosed with brain metastasis and later started the treatment with Tagrisso. It all happened very fast, when she was diagnosed 4 months ago it was stage 2. The treatment had good improvement on her syndromes and regression at tumours was found thanks to Tagrisso 80 mg. For the last 4 years she was really well, even though she was not like before she was able to her own things, take herself to the hospital, cook etc..For the last 1,5 year she was already 3 monthly scans with PET and MR. Since then she thankfully did not have any metastasis according to the MRs and PETs. But she is not well for the last 2 month and she is getting worse with a speed. She has his last brain MR scan at 1 of January and PET CT at 8 of January and they came clean! The only problem is her CA is increasing CA 15-3 is increasing. Now we do not understand what is going on because she has become 39 kilos, she is eating and having constant diarrheas, she is loosing her walking, hearing, memory loss, seeing and from today on she is having problems with motor reflexes. First CA was increased, then she started to loose weight, then she had numbness on ehr legs and started to have difficiulty to walk with balance, she walks with a staggered gait, then she started to have memory losses in only last 3 weeks.The doctor did groups of tests and could not find anything. She was on neurologists, general medicines, memory tests, paraneoplastic panel tests etc.. I can not say the doctor is great in communication either. I am sure she is a good doctor in knowledge but we live in Turkey and we are going to the state hospital. The great thing was we had to sue the state insurance company to get this medicine, and since it worked for my mother, we were entitled to receive this medicine free of charge as of December 13, 2024! we won the case! But now she is getting worse in the last weeks. She still remembers us kids but I am super worried if we are loosing her slowly. Since there is no progression on MR and CT scans what is going on? Is this the side effects of Tagrisso? Or is this how her terminal illness ends and she will leave us soon? Is there a possibility that she can get any other treatment?
I really appreciate your help, there is really no good information out there and I remember you were super helpful to us.
Thank you

In reply to by rukenk

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Hi Rukenk,

 

I'm sorry your mom has progressed in this way.  I'm unsure if I understood correctly, did her onc exclude paraneoplastic syndrome for which steroids can be used to ease symptoms?  If it's a paraneoplastic syndrome not related to cns metastases chemo may be an option. 

 

Did they look for leptomeningeal disease (when cancer cells enter the spinal fluid that bathes the brain and spinal cord)?  It can also be difficult to diagnose and no good options for treatment. Some oncologists try doubling tagrisso dose for people who may be able to withstand the side effects in hopes that the extra dose will reach, but there is no data to suggest this is helpful. 

 

I wish I had more to offer in terms of treatment options and just identifying why this is happening.  Again I'm very sorry about this complication.

 

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.

zhengchenji18
Posts: 30

Thanks for the information Janine.

His Onc also mentioned BRAF as well.
We are still waiting for his new molecular results.

Are you aware of any other potential treatment for the below.
From his past test in 2021, beside EGFR exon 19, the two significant markers are :
1. MYCL Amplification Copy number: 4.9MYCL, MYCL proto-oncogene, is a transcription factor that regulates expression of genes involved in cell cycle progression, apoptosis, and cellular transformation (PMID: 25038584). Amplification and overexpression of MYCL have been previously observed in lung cancers (COSMIC, PMID: 22941188, 23035247, 16116477, 32003251). MYCL amplification is likely oncogenic (PMID: 27298335, 24401838, 31164374, 29596783, 32003251). A preclinical study suggests MYCL amplification is predicted sensitive to Aurora kinase inhibitors in vitro (PMID: 22222631).
2. PIK3CA (NM_006218.3): c.1616C>G (p.Pro539Arg) 55%PIK3CA is an oncogene involved in cell growth, apoptosis, transformation, motility, and adhesion through activation of the PI3K/AKT/MTOR pathway (PMID: 12040186, 9759495, 15647370). The PIK3CA p.Pro539Arg variant is a gain-of-function mutation that occurs within the helical domain of the PIK3CA protein (Uniprot). This variant has previously been reported in lung cancer (COSMIC, TCGA). Functional studies suggest this variant results in increased PI3K activity in vitro (PMID: 17376864, 29533785). PIK3CA mutations are associated with shorter overall survival in lung adenocarcinoma (PMID: 24533074, 27554588). The impact of this variant in this disease site is uncertain.

In reply to by zhengchenji18

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Z,

I'm sorry but I cannot interpret this information for you.  The onc should be able to discuss any relevant info past its relationship to neuroendocrine cancers.  I hope your father is able to balance treatment and living life for as long as possible. 

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.

zhengchenji18
Posts: 30

Sorry understood I think I was asking too much.
His NGS results just came back and it’s essentially the same as 2021 report.
So no BRAF.

His only significant mutation is PIK3CA. There doesn’t seem to be any targeted therapy for him. So the only option is pemberlizumab now

In reply to by zhengchenji18

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Z,

 

Don't apologize for asking.  I don't know if you've seen our latest oncTalk forum.  There is a good discussion on sclc (small cell neuroendocrine lung cancer), which is where we base our treatment knowledge for large cell neuroendocrine lung cancer (sclc is common, large cell NE is rare. hence the research difference). 

Here is the link to the playlist.  I suggest you watch the first part of the entire forum (the forum begins with sclc).  Note that research data strongly suggests duvalumab and atezolizumab have better efficacy that pembro. 

 

I asked Dr. Aakash Desai, "Generally speaking, if that exists, when a targeted EGFR cancer turns to SCLC, or in this case, large cell neuroendocrine in the only growing tumor, is the standard of care for ES SCLC used?"  He said,  "Yes, that is correct."   The most current info available is on the OncTalk forum link above. 

 

Take care and 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.

rukenk
Posts: 10

Dear JanineT,
Thank you very much for taking the time and responding. You have really helped us understanding the situation, unfortunately of a bad situation.
Paraneoplastic panel test came negative from variety of aspects. Therefore this possibility was eliminated. It would be better at least curable.
We never heard from leptomeningeal disease untill you said it, it seems like a high probability.. and not curable..
Another possibility appaerantly is the whole brain radioiotheraphy she took at 2021 for 1 and a half month where we had to stop Tagrisso because a cardiologist because a cardiologist made the wrong diagnosis that it caused QTC interval..
Thank you a lot..

In reply to by rukenk

JanineT GRACE …
Posts: 676
GRACE Community Outreach Team

Rukenk,

Please let us know if a diagnosis has anti-cancer treatment options.  Even in this bad situation, I hope your mother, you, and your family can find peace and comfort.  If it is decided there aren't good options for anti-cancer treatment hospice should be offered to provide comfort care to your mom and family.  Keeping you in my thoughts.

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.