Tagrisso Response Duration

Portal Forums Lung/Thoracic Cancer EGFR Inhibitors Tagrisso Response Duration

This topic contains 6 replies, has 3 voices, and was last updated by  scohn 5 months, 1 week ago.

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January 7, 2018 at 3:04 pm  #1293714    

bfarz

Hi, 64 Y/O female, asian, dx 12/2011 Stage 4 Adneo del 19 egfr+, Tarceva for almost 5 years, no progression, then small progression, Almita/Carbo 4 cycles as hold over, tissue biopsy T790M + , Lepidic predominant Adeno, Started Tagrisso 12/2016, tomorrow repeat CT. How long is the longest documented duration of progression free survival for Tagrisso? Is the Lepidic predominant histology makes a difference in response to Tagrisso? Are there any good clinical trials for patients who develop resistance to Tagrisso or is it all depends on finding something that is growing to biopsy to see what the new mutation is? If only one area that is growing will SBRT be helpful and keep Tagrisso going. Sorry for so many question. Trying to be proactive. God bless you for helping .

  • This topic was modified 5 months, 2 weeks ago by  bfarz.
  • This topic was modified 5 months, 2 weeks ago by  bfarz.
January 7, 2018 at 5:03 pm  #1293717    
JimC Forum Moderator
JimC Forum Moderator

Hi bfarz,

Congratulations on the great response to Tarceva, and I hope your scan results show that Tagrisso has been effective. As with Tarceva and many other lung cancer drugs, there are cases of patients responding for a number of years, to the point where these patients “drop off” the statistics due to a lack of continued follow-up. Since Tagrisso is relatively new, that is certainly the case, and I hope that you become one of these “outlier” patients for whom the response is particularly durable.

As discussed in Dr. West’s post on lepidic predominant adenocarcinoma (still often referred to as “BAC”), this type of lung cancer can be aggressive, but it can also be “very slow growing and among the least threatening cases ever labeled as lung cancer.” At diagnosis, it’s not possible to determine how aggressive a particular patient’s cancer will be, but the passage of time helps answer that question. From the history you’ve described, your cancer appears to be slow-growing and responsive to Tarceva, so it may be that you will have a long response to Tagrisso as well.

At present, progression on second-line Tagrisso is treated with standard chemo agents or perhaps immunotherapy, as we don’t really have a good TKI to address such progression. Also, as you mention, some oncologists, in the face of a single site of progression, will radiate that site and continue the TKI.

As far as a biopsy to check for a new mutation, if there isn’t progression of sufficient size to biopsy, then there may not be a need to change therapy. And since there is no Tagrisso resistance mutation for which we have a targeted therapy, a biopsy may not provide usable information. That being said, if at some point your doctor feels a biopsy is needed, then a liquid biopsy (using bodily fluids rather than tissue) may be recommended.

But we’re hoping Tagrisso is effective for a long time!

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

January 7, 2018 at 5:15 pm  #1293719    

bfarz

Thank You for your quick amazing response. The histology was lepidic predominant invasive adenocarcinoma . Is that still considered the old BAC? or does it have to be Insitu to be like the old BAC?
Also., Are there any clinical trials for 4TH GENERATION TKI’S, AFTER TAGRISOO THAT HAVE SHOWN SOME PROMISE? even if they are not available yet.
Thank you for your love and help for all struggling with these questions.

January 8, 2018 at 7:20 am  #1293723    
JimC Forum Moderator
JimC Forum Moderator

Hi bfarz,

Dr. West has stated that most cases of BAC are not pure BAC but a mixture of BAC and a more invasive form of adenocarcinoma, sometimes referred to as “adenocarcinoma with BAC features”. Such cancers can be indolent as well. As Dr. West stated in the comments to this post:

“Adenocarcinoma with BAC features is a mix, and it can act more like a classic BAC syndrome and grow slowly in the chest only, or it can have a bit of BAC but really act like a regular invasive NSCLC (adenocarcinoma). Conventional chemo tends to work best on faster growing cancers, so I believe that some of the problem with less responsive BAC tumors is that they are so indolent that they aren’t very vulnerable to chemo. However, adeno with BAC features can be as aggressive as any other NSCLC, or pretty slow. Often how the patient is doing over time (one month to the next, for instance) and/or how much scans have changed, especially in between treatments, can give a hint.”

There is research into fourth generation EGFR TKIs, but I haven’t located any open trials at clinicaltrials.gov. One such agent is EAI045, for which I found no pending trials.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

January 8, 2018 at 11:26 pm  #1293727    

bfarz

THANK YOU. you are really amazing, your answers are so well thought of. Its clear that you read the question in detail.
Well, Prelim CT report done today showed no progression, essentially no change. So Tagrisso is to continue. I am going to make an appointment with DR WEST in the near future just to give a fresh set of eyes to look at the cancer behavior. Can the behavior suddenly change and all of a sudden behave aggressively.
Basically my question is , when resistance develops and there is a new mutation will the histology of lepidic predominant still dominate the behavior? I don’t know if I am explaining my question
Thank you for your time and God bless you

January 9, 2018 at 5:24 am  #1293729    
JimC Forum Moderator
JimC Forum Moderator

Hi bfarz,

Congratulations on the great scan report; glad that you can stick with Tagrisso and that it continues to keep your cancer under control.

If you have a mixture of indolent BAC and adenocarcinoma, there is always the possibility that the invasive component can become more aggressive, although your long history of slow/no growth makes that less likely. With any slow-growing cancer, it can be difficult to determine whether it’s the treatment that’s working well, or just the indolent nature of the cancer.

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

January 16, 2018 at 9:49 am  #1293802    

scohn

Hi Bfarz!

Glad to hear the Tagrisso is working. Hope you continue to have great response and control from it!

Just a note on 4th generation TKIs. There actually is an ongoing trial of a new TKI designed to treat the most common resistant mutations ( i.e. Exon 20 mutations) from EGFR as well as the Exon 20 mutation of HER2. It even has a test cohort of patients with more typical Exon 19/21 mutations. It is clinical trial of a drug AP32788 (originally from Ariad Pharmaceuticals, bought out by Takeda). The clinical trial number is NCT02716116. They are currently recruiting and I believe they have just entered their expansion phase (I believed they have completed their dose determination phase) and will be beginning to accept patients at new sites. This is the trial my wife is approved for, but they are holding off for now since she is responding well to gemcitibine.

All the best to you for continued great control from Tagrisso!

scohn


Wife, lifelong non-smoker, dx 4/24/15 adeno NSCLC stage IV, poorly diff. 2 bone mets, 1 lymph node. HER2 Exon 20 mutation. 6x Carbo/Alimta – >50% reduction in primary tumor, lymph nodes, & bone. Alimta maint. not effective, tumor growth, new liver mets. 11/15 – Opdivo; Not effective-add’l growth. 4/16 – clinical trial drug, large reduction of tumor and mets. 11/16-tumor growth, liver mets stable. 2/17-All Stable. 8/17- Add’l growth-off trial, 9/17 Gemzar- tumor reduction, then stable.

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