Progression on Tagrisso having original mutation L858R

Fri, 11/15/2019 - 08:46

Dear Doctors and Moderators!

could you please advise where to go after dramatic progression in bones and lungs on Tagrisso .

first line: carboplatin alimta avastin didn’t work at all

second line: tarceva worked perfectly for 9 months them progressed in lung and bones

third line: Tagrisso without t790m worked perfectly and clear both lungs for 5 months 

now is dramatic progression in bones and lungs .

Tissue biopsy showed my original l858r mutation. 

Could you please advise what could be the next. I am afraid to start chemo again because the first one didn’t work for me .

many thanks in advance ❤️



JanineT Forum …

Hi Vera,


Welcome! I'm so sorry to hear about the progression. Give me a bit to get back with some resources.


All the best,


JanineT Forum …

Oh Vera I'm so sorry I didn't get back with you. 


In this video Dr. West and Dr. Yu discuss tki including options after tagrisso.  The entire video is good but for you at 45 minutes on the video Dr. Yu speaks about resistance to tagrisso.  Including the importance of tissue biopsy the new progression to look for new mutations such as MET and c797s or change in the type of cancer such as the unusual change from adenocarcinoma to sclc all of these can dictate type of treatment that will be the best for you.  At about 37 minutes Dr. West talks about the dangers of immunotherapy for those with egfr (it's likely a sequence issue but dif something to consider beforehand). Don't miss the q and a.

If you're not already being seen by one it probably is best to get a 2nd opinion from a lung cancer specialist in a large teaching/research facility who will have the most up to date information on your specific situation.  Unless you choose a clinical trial you could most likely continue treatment with your local oncologist.  Here is one of my favorite articles on the subject


I hope this is helpful and keep us posted.

All the best,





Thank you, Janine for all information. My tissue and blood biopsy showed that I still have adeno with my original mutation l858r anD nothing else.

what is about afatinib plus cetuximab?

thank you.


JanineT Forum …

If you didn't respond at all to the chemo you're right you probably won't respond to another chemo drug.  But just because you didn't respond "well" doesn't mean another single chemo agent won't have some efficacy.  Abraxane is a good all around nsclc chemo as well as gemzar.


Afatinib plus cetuximab has a high toxicity profile.  Here is an old forum that discusses the experiences of some who were in the trial.  At 34 minutes of the RET/MET/BRAF video below Dr. Sabari mentions his use of this combo. Note that you'd want to talk to your onc about appropriateness. 

Here is an excellent video “RET/MET/BRAF: initial treatment, acquired resistance, Q&A Joshua Sabari, MD Joshua Bauml, MD

At 28 minutes they discuss how different types of testing will give different answers such as FISH test for MET amplification and immunohistochemistry testing for HER2.  The difference in these tests is above my paygrade but if you want a deep dive that’s what google is for. :) But they are different from broad mutation testing often given. These MET and HER2 tests would probably be given for possible entry into clinical trials.

At 13 minutes on this video the doctors talk about ATOMIC run by Dr. Ross Camidgege.

ATOMIC is a large consortium of facilities participating in collecting information about acquired resistance.  If I were a person looking for the most up to date ideas on treatment options in your type situation I would look to the doctors who are participating in ATOMIC.  The reason I think a 2nd opinion from one of these doctors is worthwhile is they specifically treat people with acquired resistance, they are actively working with other institutions who do the same.  So there are lots of heads thinking, treating, and talking about your type of situation.  They will be the ones in the know.

I hope this is helpful,



I know I just keep heaping info on top of the other but I wanted to link the other videos from the 2019 targeted therapies patient forum.  Q and A and Challenges and Opportunities