Afatinib after progression on osimertinib

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Afatinib after progression on osimertinib

Dear Doctors and Moderators,

  I have been on tarceva for 9 months and after progression and high toxicity moved to Tagrisso. Blood biopsy showed same l858r mutation, but no t790m one. My question is: if I progressed on osimertinib but keeping same original mutation, can I try afatinib?  Or Tagrisso plus afatinib combo? Or Tagrisso plus avastin? Retry tarceva plus Tagrisso combo?

Thank you very much for your assistance.



Jim C Forum Mod...
Jim C Forum Moderator's picture
Afatinib after progression on osimertinib

Hi Vera,


First, let's hope that you don't face the question of progression on Tagrisso for a long time. But if that time comes, it's difficult to say what may be effective in such a third-line setting. We do know that returning to a prior agent such as Tarceva can result in a limited response in some patients. Also, for the most part patients who previously progressed on Tarceva don't often respond well to single-agent Afatinib, although a significant subset of such patients will get a good response to the combination of Afatinib and Cetuximab. The downside of the combination therapy is that it can have a very challenging side effect profile. But in general, the use of a second-generation EGFR TKI is preferred after progression on a first-generation TKI.


Adding Avastin to EGFR TKI therapy has some adherents, but whether it generally provides an added benefit is not established. On the other hand, standard chemotherapy is an option that should not be ignored, as many patients who respond to EGFR TKIs also respond well to chemo.


Hope you have a great response on Tagrisso!


Jim C Forum Moderator



Afatinib after progression on osimertinib

Thank you , Jim for your valuable response.  I just thought probably I can buy more time by switching from Tagrisso to afatinib now when I still have my l858r mutation and not t790m. In addition afatinib can cause t790m mutation later on and then I can get back to Tagrisso.....

May be it doesn’t make any sense.....

warm regards


JanineT Forum M...
Hi Vera, I hope tagrisso has

Hi Vera,


I hope tagrisso has fewing side effects and you're feeling better.  If tagrisso is working then it is your best bet to stay the course.  I get your reasoning but logical thinking too often doesn't work in anti cancer treatment.  If tagrisso is working you wouldn't want to add on another drug that might be helpful down the line(s).


I hope you won't need to make any changes for a long long time,


Hello !My mother was

Hello !

My mother was diagnosed with stage 4 lung cancer in jan 2018. She was on osimertinib then which stopped showing much control after 10 months. We later did light chemo for pleural effusion . Now we are wondering if we can do afatinib  . As she is still EGFR exon 21 positive along with MET positive ( for which we tried Crizoltinib whicuh didn't work).

Can I please know what you . Waiting for your reply!

Thank you,



JanineT Forum M...
Hi and welcome to Grace.  I'm

Hi and welcome to Grace.  I'm so sorry your mother is having to deal with this.  If she has only had 10 months tagrisso and a bit of chemo in 2 1/2 years it sounds like her cancer is rather slow growing.  That's good.  I've asked one of our faculty for up to date intel on the sequencing of treatment lines such as your mother's.  We should hear back within a day.  It's a young question that I don't think has one clear standard of care option.

I hope your mother can keep her cancer at bay for a long time.

Best of luck,


Thank you so much for the

Thank you so much for the reply! I will wait for any suggestions!


JanineT Forum M...
Information from2019 Case Based Studies and 2019 Targeted Therap

While we wait to see if Dr. West has new input let me share some excellent info.  At around the 45 minute mark in this video, the discussion turns to acquired resistance. This video is part of a set from the 2019 Targeted Therapies Patient Forum. 

Have the newer met inhibitor?

At 1 hour and 13 minutes there is discussion about trying 1st and 2nd generation tki after progression on tagrisso.  It should be on your list of possible lines of treatment.


Chemotherapy can work well for those with mutations like egfr.  Carboplatin plus alimta with or without avastin then after 4 to 6 cycles remove the carbo and continue with alimta with or without avastin can be very efficacious and alimta has a better side effect profile than other chemotherapies. 

Another discussion EGFR Mutation & MET - Treatment Decisions, Level of MET Amplification   The discussion about the level of met amp and may be more informative than helping find the next treatment.

Another video in this case base series on the subject.


Unless there is more up to date info these 2 series' are about as informative as you can get. 


I hope this is helpful,




Okay thank you for these

Okay thank you for these suggestions.  When my mom had pleural effusion we had tried that chemo combo on low dose and it was helpful . So can we try it again ? Will it be effective still ?

Here doc is suggesting combining immuno  and chemo  ( a differen tcombo). I want to keep that for the last .. 

JanineT Forum M...
Right, waiting until the last

Right, waiting until the last lines of treatment before trying immunotherapy is safest.  There is the possibility of dangerous bouts of pneumonitis if a tki is taken after immunotherapy.


Yes, it should be fine to try chemo again with the hope that it will be effective.  The reason one only takes 4 to 6 cycles of platinum-based chemo is that it tends to cause allergic reactions after that.  However, if it's been over a year or so her onc may deam it safe to try again. 


There are several chemo drugs that people with nsclc take in succession that have efficacy after the previous stops working.  So there should be options of a chemo drug to pair with immunotherapy.


I hope your mother does well


JanineT Forum M...
Dr. West responded via email

Dr. West responded via email.

He stated, "There is no utility for afatinib after Tagrisso.

There is a possibility of finding a new target by doing a repeat biopsy of a progressing area of disease -- that's not common, but possible. 
The main treatment approach after progression on Tagrisso is chemo, potentially with Avastin and/or immunotherapy added to it.  But Tagrisso is the most effective EGFR inhibitor we've got, so there really isn't any established or even anticipated value in trying a different, less effective EGFR inhibitor after that. The only possible exception is if a patient has a biopsy of a progressing lesion that shows an EGFR C797S mutation, which can respond to a first generation EGFR inhibitor like Iressa (gefitinib) or Tarceva (erlotinib).
There's a whole lecture on this topic in the targeted therapies forums we've done. Last year the EGFR session was by me and Helena Yu -- I can't remember which of us did first line and which did 2nd line. The second line would cover options after Tagrisso."
Dr. West's mention of the lectures is linked in a previous post. 
Take care,
Thabk you very much for this.

Thank you very much for this. 

So she will be doing Avastin in combination with genoxel from monday.Alongside we will do a biopsy.  And check of she can get any other medication instead.

Thank you Janine!

Sending lots of love your way. :) 

JanineT Forum M...
Hi Ramya,  I'm very happy to

Hi Ramya,  I'm very happy to be of help.  I hope your mother does well on the new treatment.

Lots of love sent back your way. :)