Hello everyone,
So mom is currently in hospital given IV steroids to help resolve her highly suspected "Tagrisso induced pneumonitis". Earlier this week mom's SPO2 was reduced, heart rate elevated, and blood pressure dropped. No fever or cough. She remains on supplemental O2 to help her shortness of breathe.
We were told that if this is indeed pneumonitis caused by Tagrisso, then mom will most likely be off the Tagrisso. This is heart breaking, as we have gone through so much to access this medication, and it seems to be working very well for her in order to control the rapid progressions in her brain. We are afraid that once the lung issue resolves she will no longer have any viable treatment options to treat her disease in the brain with apparent leptomeningeal involvement.
I just wanted to provide an update on mom's situation, and hoping that someone can offer some insight or suggestions on what to do next. Here is her cancer journey history.
- June 2013 - Feb 2015 => Iressa
- Feb 2015 - Dec 2015=> CO-1686
- Jan 2015 => Afatinib (2 weeks on it while waiting for Tagrisso approval, did fairly well)
- End of Jan 2015 => Tagrisso (stopped 4 days ago)
Here are the treatment options I am thinking:
- Rechallenge Tagrisso at 80mg (previously on 160mg)
- Restart Afatinib
- Immunotherapy (e.g., Opdivo, Keytruda?)
- pulsed Tarceva?
- standard chemo??
- anything else I haven't considered??
*I'm afraid she might be too weak to be considered for clinical trials? Not sure...
Looking forward to hearing back with any suggestions, thanks so much in advance!
God bless,
Hain
Reply # - February 20, 2016, 12:02 PM
Hi Hain,
Hi Hain,
I'm so sorry your mom is going through this terrible stint and hope she will be better soon. Tarceva isn't usually used after after definitive progression. All other suggestions you mentioned are shown to have efficacy for nsclc in 2nd and later lines of treatment. Immunotherapies have occasionally been thought to be the reason for inflammation in the chest so that may not be a first choice. A break to get a chance to feel better would also be an option if that is possible. However none of that addresses lepto though there's just no good treatment for that.
I hope your mom is comfortable and heals from the pneumonitis.
Always hoping for the best,
Janine
Reply # - February 26, 2016, 08:58 AM
Thank you Janine,
Thank you Janine,
So mom is currently in hospital recovering slowly from the pneumonitis - should be discharged in a few days soon. Once the lung resolves, I am still very curious what a doctor on this forum's opinions are in terms of next treatment option? e.g., resume Tagrisso on a lowered dose? (previously 160mg daily for 3 weeks). Or try one of the above treatment I proposed (e.g., Afatinib, immunotherapy, some others?). I'm sure there's not evidenced-based treatment choice at the moment but just wanted to get a good opinion prior to discussing options with mom's primary oncologist.
On a side note, the most recent brain MRI showed significant reduction in tumor and lepto disease 1 month starting Tagrisso - from numerous spots to very few spots. She has also been asymptomatic in terms of headaches and brain symptoms since starting treatment. Given this, is it worth rechallenging Tagrisso at a lowered dose?
Looking forward to hearing back and thank you in advance!
Best,
hain
Reply # - February 26, 2016, 02:47 PM
hain,
hain,
Is your mom taking pulsed tagrisso? It might inform the doctor's comments.
Janine
Reply # - February 26, 2016, 04:00 PM
Hi Janine,
Hi Janine,
My mom was on Tagrisso at 160mg daily dose for 3 weeks, at which her pneumonitis seemed to be causing issues. She has been off Tagrisso for the past 1.5 weeks recovering her oxygen saturation, given IV steroids.
If there is any more info that is needed please let me know! Really looking forward to a reply. As always, many thanks for hosting an invaluable platform.
Sincerely,
Hain
Reply # - February 27, 2016, 06:27 AM
Hi Hain,
Hi Hain,
Unfortunately, the recommendation in the Tagrisso Prescribing Information is to discontinue Tagrisso permanently if interstitial lung disease (ILD)/pneumonitis is confirmed. That is the same recommendation for Tarceva, and resuming Tagrisso at a reduced dosage would be very risky. The issue of rechallenging Tarceva after it has caused ILD is discussed here.
One question: was there a scan after treatment with Afatinib? If not, perhaps some/all of her improvement may be attributable to Afatinib, which might make rechallenging with that drug more tempting.
Good luck.
JimC
Forum moderator
Reply # - February 28, 2016, 11:29 PM
Hi Jim,
Hi Jim,
Thank you for the reply. I understand that the recommended course of action in the product monograph of Tagrisso if pneumonitis is diagnosed would be to discontinue; however, I also know that there has been case reports from the literature suggesting that rechallenge of a TKI after a short break after drug-induced pneumonitis could be beneficial in some patients, especially if those patients do not have many viable treatment options for their cancer.
e.g:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184641/
http://www.ncbi.nlm.nih.gov/pubmed/23410901
In my mom's case, we know that she was experiencing progressive brain mets and leptomeningeal involvement which occured in a matter of weeks. Also, I understand that there aren't too many effective treatment options for patients with brian mets, especially those with leptomeningeal involvment. Given this information, wouldn't it be especially important to take the risk of a second episode of drug induced penumonitis (potentially fatal) instead of taking the alternative which is for sure experience progressive brain disease and definitely fatal?
To answer your question Jim, no there were no scans tkaen after start of Afatinib; however, mom was starting to feel much better gradually while on Afatinib for the 2 weeks time. Then she started Tagrisso, which I believe continued to help her improve after start of Afatinib. Mom had a recent brain MRI which showed siniificant reduce in brian disease and lepto.
Best,
Hain
Reply # - February 29, 2016, 09:22 AM
Hi Hain,
Hi Hain,
I think what you suggest is very reasonable. As you say, there simply are no established treatments for LMC, so the risk may be acceptable under these circumstances.
Since your mom had only been on Afatinib for a couple weeks, I expected that there hadn't been a scan before starting Tagrisso. That raises the possibility that her improvement was due to Afatinib (or both), so those might be the two best options for her at this point.
Good luck with whichever of them is chosen.
JimC
Forum moderator
Reply # - March 1, 2016, 09:04 PM
Hi Jim,
Hi Jim,
Thanks for the reply and affirmation that my thoughts for options moving forward are reasonable. Just wondering would it be possible for a doctor on this forum to just make a comment on what options they would consider for their own patients, who present similarly as my mom, given her cancer history?
I am under the suspicion from conversations last week that the onc is not likely considering rechallenging with Tagrisso because of the issues with drug induced pneumonitis. When asked about Afatinib or immunotherapy, he mentioned that any generation TKIs and immunotherapy could also induce a similar side effect. Given this, what other options are we to consider that would help control her disease in the brain, bones, and lungs?? Is the risk not justified by the fact that there is just no other viable treatment options available?
On a side note, mom has never had any lines of conventional IV chemotherapy - would this be a viable option? I read in literature that chemo tends to only extend life by a couple months and tends to not work well on the brain or leptomeningeal disease. Is this accurate? If so, is it at least worth trying out on how she responds and if there is no clinical response in the short run, then retry TKI therapy (e.g., Afatinib?). Or is it more wise to pursue rechallenging TKI or immunotherapy or some other therapy I haven't thought of?
Really confused and looking forward to any help and guidance possible. Looking forward to hearing back!
Best,
Hain
Reply # - March 2, 2016, 02:12 PM
As you likely know, the
As you likely know, the treatment options in people with leptomeningeal carcinomatosis (LMC) and who are debilitated by their disease are very limited -- there is really no treatment that has any clear efficacy and that is commonly recommended. As you also know, EGFR-directed therapies are likely to be the overwhelmingly most fruitful approaches, but if she is unable to tolerate Tagrisso (osimertinib) because of pneumonitis, I think there is good reason to be extremely wary about trying it again. Certainly, pulsed Tarceva (erlotinib) is a treatment approach that has some success in EGFR mutation-positive patients with LMC and could possibly be of benefit, but we really don't know if it would lead to worsening of pneumonitis induced previously by Tagrisso.
As for chemo, that is certainly a potential consideration, but I would be concerned that if she is possibly being considered by you his 2 week for a clinical trial, it is likely for the same reason that she is not a good candidate for chemotherapy. I would really be disinclined to favor chemotherapy and somebody was not getting out of the house and walking into the oncology clinic without assistance.
Good luck.
-Dr. West
Reply # - March 2, 2016, 11:49 PM
Hello Dr. West,
Hello Dr. West,
Thank you very much for your response! It is my understanding that you are leaning towards treatment options that involve EGFR-directed therapy, whether it is rechallenging with Tagrisso or Pulsed-Tarceva, and IV chemotherapy is less likely the treatment choice due to tolerability in patients who are debilitated by their disease.
I am curious what your thoughts of are in terms of immunotherapy, such as from Opdivo or Keytruda? Is it something that you would also consider in this setting of patient as next line therapy should either EGFR therapy not be available for whatever the reason? Also, besides those that I have considered, do you know of any other possible treatment options? The LMC has never been officially diagnosed via CSF cytology, it has only been reported in radiographs (brain MRI as leptomengeal spread etc.), along with clinical weakness, is this even enough to be confident she has leptomeningeal disease?
Thanks so much for the reply in advance!
Best regards,
Hain
Reply # - March 16, 2016, 04:27 PM
Hi everyone,
Hi everyone,
1 month later from drug-induced pneumonitis, and having stopped Tagrisso for 4 weeks now (restarted Afatinib 1 week ago), the lung is still worsening in terms of disease process. Can this still be due to pneumonitis that is out of control? Infections have been ruled out due to 2 unsuccessful bronchoscopy and cultures, been on a 1 week course of broad spectrum antibiotics (Septra) for unusual infections, continue to be on high dose steroids (methylprednisone)- with gradual decline in lung functions.
The hospital team seem to have given up - and I have considered comfort care only, but I don't want to lose my mom to a side effect or to a lung issue that is still not 100% clear with the medical team.
Does anyone have any light to shed or evidence in terms of how long to wait it out before pneumonitis might clear? Is 1 month the maximum? Why does the lung keep deteriorating despite being off the drug that is suspected to have caused this insult? Any alternative therapies to help settle this out of control inflammatory process?
-hain
Reply # - March 16, 2016, 11:09 PM
Hain,
Hain,
I don't have an answer for you. I am sorry that your mom's condition has worsened. I will pray for you and your mom that things will turn around soon.
Emily
Reply # - March 17, 2016, 05:32 AM
Hain,
Hain,
I'm sorry to hear about the continuing and worsening lung disease. In his comment above, Dr. West raised the concern that pulsed Tarceva might worsen the drug-induced pneumonitis. Since afatinib can also cause pneumonitis, that may be what is preventing her recovery from it, and you may want to consider discontinuing it to see if that helps. I wish I could suggest a good treatment alternative in its place, but as Dr. West said your mom may not be well enough to be able to tolerate chemotherapy.
Sending positive thoughts to you and your mom,
JimC
Forum moderator
Reply # - March 19, 2016, 01:51 AM
Thanks for reply guys. Mom is
Thanks for reply guys. Mom is in hospital palliative care and is dying of pneumonitis drug induced. My advice to all: consider asking for a stronger dose steroids if after a week or so you still develop progressively worsening lung function because it only gets worse. Not sure why dose was kept the same for 4 weeks if there is a trend towards worsening. I know we were waiting on bronch aND culture results but in the meantime doesn't it make sense to give higher dose steroids if the current dose isn't effective?
Reply # - March 19, 2016, 08:22 AM
Hain,
Hain,
I am so very sorry to hear this sad news about your Mom. Unfortunately, EGFR TKI-induced pneumonitis is often fatal despite discontinuation of the TKI and initiation of steroids. Whether a higher dose of steroids would have helped is very difficult to know. I have found that second-guessing treatment choices can be very tempting, but although the alternative treatment always works better in theory than that used in reality, that is just conjecture. With TKI-induced pneumonitis, the damage is often irreparable, and no amount of steroid treatment can reverse it.
My thoughts are with you and your Mom.
JimC
Forum moderator