AZD9291/Tagrisso No Response T790m positive - 1273898

coco1
Posts:19

My mother was diagnosed in 2013 with stage IV NSCL cancer in lung and lymph nodes (never smoker, healthy. On Tarceva for 2 years with a good quality of life initial shrinkage of tumour, holding and then increase, biopsy done for AZD9291, T790m positive. Fluid drained quickly with tap at same time as biopsy on rib, in great pain afterwards, in hospital 3 times for more fluid to be drained finally drain inserted in left lung, caught infection (due to procedure or being in respiratory wards with people who had pneumonia, etc!?), was not well enough for trial, trial closed in summer 2015. Was in hospital for a month. We did not realise until later that she was very ill at that point due to the hospital caught infection. We didn’t know full details but was told that the cancer had spread to her bones. She had three rounds of chemotherapy (1 round of permextred, 2 of permextred and carboplatin), her oncologist put her back on tarceva to help kill off any cells that had not developed resistance (I’m not sure if this works or not). We were told that the chemotherapy had worked but her oncologist didn’t want to put her through any more. From about October to January, she was waiting to get AZD9291 on compassionate grounds and then through the early access scheme.
Before I go back to her I would really appreciate if there anyone else who has the T790m mutation but tagrisso was not effective? Those in the 30%? If it was the cancer that was causing her fatigue, etc surely more chemotherapy or some other drug would have been an option to control the cancer before it got even more advanced. She said immunotherapy would have needed all the paperwork, etc and AZD9291 looked like the best option, I know I can’t bring her back but for my sanity, I need to know. She has 4 other people who got on the AZD9291 trial and are doing fine. My parents did think about private treatment at the beginning but we were told the expertise was in the NHS. Opinions from Europe and US welcome. Thank

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Reply # - May 5, 2016, 02:59 PM

catdander
Posts:

Hi coco1,

Studies have shown that around half of people who are egfr and T790M positive respond well to tagrisso. Even with those numbers there are people who remain have less but real efficacy and stability with the drug. It's probable that tagrisso is the best option if it is indeed an option through NHS. I would push for it.

I hope she responds to treatment.
All best,
Janine

Reply # - May 6, 2016, 04:18 AM

coco1
Posts: 19

Hi Janine,
Thanks for your response but due to the word limit, I was unable to make it clear that Mum tragically passed away at the end of February whilst on Tagrisso/AZD9291 for about a month. My question really is for gaining some sort of closure. I noticed on another forum and from research that the response rate to tagrisso is 70% for those who are T790m positive and so we really thought it would work for her. When I met her oncologist after she passed away, she said that my mother might have been in the 30% for whom it doesn’t work as the cancer had become aggressive after erlotinib. I just wonder if there have been many cases where patients have been T790m positive but tagrisso hasn’t worked as all I can find is positive findings. I just wonder if the cancer was allowed the progress and if she had got the drug earlier it would have made a difference? Perhaps more chemotherapy, etc. The link you posted seems to be more for those who are T790m negative. Advice appreciated, thanks

Reply # - May 9, 2016, 10:49 AM

catdander
Posts:

I'm so very sorry you've lost you mom. I know it's such a difficult thing to go through.
A 70% response rate means 7 out of every 10 people responded unfortunately 3 out of those 10 did not. It sounds as if you mom was one of the 3.

I hope for you peace,
Janine

Reply # - May 9, 2016, 11:17 AM

coco1
Posts: 19

I understand the 70% response rate, but I have not seen any posts online of people who did not find tagrisso effective who tested positive for T790m? I was looking to see if there were any other experiences? I wonder if she just received the drug too late.

I know it is unfair, no one deserves to lose their mother when they're 25.

Reply # - May 9, 2016, 07:35 PM

JimC
Posts: 2753

coco1,

I am very sorry to hear of the loss of your dear mom. Cancer is an evil disease, the behavior of which sometimes just cannot be explained. I've been active on GRACE for eight years, and have seen patients whose cancer does not respond to any treatment, and those who seem to be cruising along for years on a variety of therapies, only to succumb in a short period to cancer that has turned extremely aggressive. No one is certain why this happens.

I can't point you to specific posts by patients with T790M mutations who did not respond to Tagrisso, but the statistics from clinical trials say that they exist. Even the best targeted therapies do not achieve 100% efficacy. I can tell you that virtually everyone who loses a loved one to cancer contemplates the "what-ifs" of treatment choices (I certainly did), but sometimes cancer is just much tougher than our best treatments. In our minds, the paths not taken always lead to better results, but that's not reality.

I understand how you must be feeling. I lost my dad when I was 27, my mom ten years later, and my wife of thirty years to lung cancer almost five years ago. As you say, it's unfair, and I'm sorry it happened to you. My heart goes out to you, and my wish is that you can find peace and comfort in the days ahead.

JimC
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Reply # - May 13, 2016, 02:27 PM

kempten
Posts: 128

Hello
I'm not sure if this information applies to your mother's circumstances but I just discovered this paper.
This is just an excerpt of a longer study.
I also want to express how sorry I am about your mothers passing.

" If the
C797S and T790M mutations are in trans, cells will be resistant to third generation EGFR TKIs,
but will be sensitive to a combination of first and third generation TKIs. If the mutations are in
cis, no EGFR TKIs alone or in combination can suppress activity. If C797S develops in cells
wild type for T790 (when third generation TKIs are administered in the first line setting), the cells
are resistant to third generation TKIs, but retain sensitivity to first generation TKIs.
Conclusions: Mutation of C797S in EGFR is a novel mechanism of acquired resistance
to third generation TKIs. The context in which the C797S develops with respect to the other
EGFR alleles impacts the efficacy of subsequent treatments.
Research ,"

May be the experts can give their opinion if testing for cis and trans positions could be helpful before starting TKI therapy?

Thank you
Kempten

Reply # - May 17, 2016, 07:25 AM

coco1
Posts: 19

Hi Kempten, thanks for your response.

In layman’s terms, are you saying that if the mutations are on the same allele or in cis, AZD9291 will not work at all, even before developing resistance? If erlotinib is first generation TKI, is chemo like permextred and carboplatin second and AZD9291/Tagrisso third? C797Cs is a mutation which is not currently tested for but if it was, it could tell if it would be effective or not?

Thanks

Reply # - May 17, 2016, 08:04 AM

kempten
Posts: 128

Hello Coco1,

I'm sorry I can not answer your question in detail, since I'm a lay person without a physicians background.
As far as I understood the study : they tried to predict the next mutations, instead of waiting for the results in the patient trials. They where able to do this with their scientific method ? more complicated than I can comprehend- that is, I guess, quite reliable.
They found out which new mutations occur during Tagrisso Therapy.
They state, that the position / allele ( cis or trans ) will impact how effective Tagrisso is likely to be as a single agent or in combination with the older TKI's.
The newest generation of genetic testing might be able to tell you this, but as far as I know, this is not
( yet) done routinely.
Please, take all of this with a grain of salt, again I'm not a professional and don't REALLY know what I'm talking about.
Sorry for the limited information.
If I can find the paper again ,I will send you a link.
thanks
Kempten

Reply # - May 17, 2016, 05:54 PM

JimC
Posts: 2753

Hi Kempten,

It looks like this is the article to which you refer: http://clincancerres.aacrjournals.org/content/21/17/3924.full The most important factor to note is that this research was performed in the lab using cultured cancer cells rather than in human patients. A great many seeming breakthroughs work in the lab or in animal models, but not with humans. Although it is interesting research and may lead to treatment advances in the future, at this point it is at a preliminary stage and probably not likely to influence current treatment decisions.

JimC
Forum moderator

Reply # - May 17, 2016, 06:37 PM

kempten
Posts: 128

Hello Jim,
yes , this is the study.
Thank you for your comment.
I found it very interesting and hope it will contribute to a better understanding on what therapy might follow 3rd generation TKI therapy.
Kempten

Reply # - May 20, 2016, 07:40 AM

coco1
Posts: 19

Hi Jim/Kempten,

I guess this still might be a way to explain though not only what therapy follows AZD9291/Tagrisso but why AZD9291/Tagrisso may not work for certain individuals?

My fear is that the oncologist may just have been wanting to placate me and Mum was perhaps not in the 30% but if Mum had got the drug earlier it might have worked!? Or if she had continued on chemotherapy to try and shrink more of the cancer.

We were just so sure the drug would be helping (although in retrospect she wasn't getting better) that I didn't even think as to why the nurses called us back to the hospital and didn't believe she was dying. My Dad and I left thinking she would see another day and she was gone.

Reply # - June 14, 2016, 11:59 AM

sunday
Posts: 9

Hi Coco1,

Sorry to hear about your Mom. I am 790M positive and Tagrisso has not worked for me. After waiting for 3 months for the wonder drug to work, my oncologists team suggested me to get another lung biopsy to see new mutations. May be your Mom, like me, might have acquired another mutation. But this is not easy to figure out and takes time. After rebiopsy, the next treatment options would be to get chemo or enrolled in clinical trial.

Take care.

Reply # - June 16, 2016, 05:05 AM

coco1
Posts: 19

Hi Sunday,

Thanks for your reply, sorry to hear that Tagrisso has not worked for you. Do your oncologists think you acquired another mutation alongside the T790m which means Tagrisso does not work at all rather than the T790m mutation having changed?

Have you had your pleural effusion drained? Had it been building up?

Thank you, best of luck with treatment, would the clinical trial be immunotherapy?

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