Progression on Tagrisso (Osimertinib)

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

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 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

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

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

 : ) 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.

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

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. 

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

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

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

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

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

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

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 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."

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