Progression on Tagrisso (Osimertinib)

15 posts / 0 new
Last post
zhengchenji18
Progression on Tagrisso (Osimertinib)

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 Forum M...
Hi zhengchenji, Welcome to

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

 

zhengchenji18
Appreciate your comment and i

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 Forum M...
In the first minute of this

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

Dr West
I would say that progression

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

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

zhengchenji18
First of all, thanks to Dr

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 Forum M...
The 3 months wait and see

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

 

 

Jim C Forum Mod...
Jim C Forum Moderator's picture
Progression on Tagrisso (Osimertinib)

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 Forum M...
 : ) And that's why 2 heads

 : ) 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.

zhengchenji18
That's very clear! Thank you

That's very clear! Thank you both so much, really appreciated!

zhengchenji18
Thanks for your help in

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 Forum M...
Hi Chen, Happy New Year to

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

JanineT Forum M...
video on liquid biopsy (blood

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. 

 

zhengchenji18
Thanks again for all the help

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 Forum M...
Hi Chen, It sounds like your

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