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

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,

Ramya 

India

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,

Janine

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,

Janine

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

Janine

Dr. West responded via email.

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

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. :) 

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. :)