Any hope after Tagrisso? - 1289426

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kkh130
Any hope after Tagrisso? - 1289426

Hello,

My dad's lung tumor progressed a lot in 3 months (from 2.9 x 2.8 to 14.6 x 3.5cm) while on Tagrisso. He has t790m mutation and has been on Tagrisso since July. I would like to know if any NEW clinical trials available now to target his mutation?(where?) Is it necessary to do re-biospy?
his treatment history:
1. Tarceva for 9 months
2. CO1686 for 7 months --> progressed to leptomeningeal metastases
3. tarceva pulse + carbo/alimta/avastin for 7 months (brain met stable)
4. Tagrisso for 5 months (2-month MRI stable; no MRI scheduled this time, but no significant neurological symptoms)

Because my dad has history of leptomeningeal metastases, I would like to know if Tagrisso can be used in combination with Opdivo or chemo? How about Tarceva Pulse with Opdivo? What is the most recent clinical data for immunotherapy on patients with EGFR mutation? Should he consider chemo first before immunotherapy if immunotherapy is not effective on EGFR+? Any suggestions on the chemo drugs?

Any feedback and suggestion is greatly appreciated.

Thanks

kkh

catdander
Hi and welcome to Grace. I'm

Hi and welcome to Grace. I'm very sorry your dad is going through this.
If your dad didn't progress on alimta it can be effective for quite some time especially it seems for those with an egfr mutation. It appears to be one if not the easiest chemo drugs to tolerate. As for clinical trials it may be difficult to find a trial that accepts someone with a leptomeningeal diagnosis. However there are studies that do accept people with that diagnosis. It really depends on what exactly the trial is looking to answer and there is a growing number of trials that are looking specifically at treatment that includes cns progression.

The best way to find a trial is to see an oncologist at a large teaching/research center that does a lot of clinical trials on lung cancer. These oncologists are in the loop of what's going on where and are very helpful in paring people with an appropriate trial even if it's not theirs. Another way to find trials is to do a search on the data base clinicaltrials.org You can tailor the search in a number of ways by using the advanced search feature.

Immunotherapies haven't shown much promise in people with a single driver mutation like egfr with t790m. Though you may find some trials using combos of drugs it's important to keep in mind the added and sometime harmful side effects combining them can do. Within a clinical trial a person is watched very closely for side effects that can become more harmful than helpful. So a trial is a good place to try a combo.

I will keep eyes open for more info on the most promising trials. There's a large lung cancer conference happening that some of our faculty are attending. Those who didn't attend are loaded down covering for those who did so our resources for oncologist comment is very low at the moment.

All best,
Janine

catdander
An important addition I

An important addition I forgot to ask. Is your dad's progression in just the one tumor. That probably means tagrisso is still working in the rest of his body. The newest thought on treating this type of progression (oligoprogression) and in clinical trials is to treat locally such as radiation, even sbrt if appropriate. There are several pieces on that here on Grace. Although there are still trials going on it is very appropriate to look into this type of treatment outside a trial. The most recent and up to date, http://cancergrace.org/lung/tag/oligoprogression/

I hope this helps,
Janine

kkh130
Thanks for the response. The

Thanks for the response. The progression is not just on one tumor. There are numerous new nodules showing up on the scan. He did progress on alimta before starting on tagrisso.
I want to know if the combination of tarceva pulse + immunotherapy or tagrisso + immunotherapy or tagrisso + chemo can be used. Any doctors here actually used this combo on their patients? Will that have a better result than immunotherapy alone for EGFR+ patients even though showing progression on TKI?
What other treatment options available for my dad? Please point us to the right direction.

Thanks,

Kkh

kkh130
One year ago 2015 he had

One year ago 2015 he had Guardant360 blood test. It showed gene mutation JAK2 (V617F), EGFR (L747_P753 DelinsS), TP53 (C277F), and MAP2K2 (E66k). I don't know how reliable/accurate this test is because his t790m mutation didn't show up on this report. I do not know if he gets more mutations now after one year. Will this make any difference on how he may respond to immunotherapy? I don't feel comfortable for him to use immunotherapy alone when knowing It is not effective for EGFR+.

Thanks,

Kkh

JimC
Hi Kkh,

Hi Kkh,

It's very likely that the T790M mutation developed during the course of treatment; that mutation is the cause of a large percentage of EGFR+ lung cancers developing resistance to EGFR TKIs.

There is not much reason to expect that the presence of the T790M mutation would affect response to immunotherapy.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

kempten
Hello kkh,

Hello kkh,

I found this clinical trial while searching for my own next potential therapy :

NEW CLINICAL TRIAL

NSCLC and brain or leptomeningeal metastases
Kadmon (NCT 02616393):
A Phase 2, Multicenter Study of Tesevatinib in Subjects With Non-Small Cell Lung Cancer, EGFR Activating Mutation, Prior Treatment With a Tyrosine Kinase Inhibitor, and Brain Metastases or Leptomeningeal Metastases. Download pdf flyer

I think a tissue biopsy is necessary to take part.

Not sure if this might be a possibility for your father.
Wishing you all the best

Kempten

catdander
Thanks for sharing your work

Thanks for sharing your work Kempten!

kkh130
Hello Kempten,

Hello Kempten,

Thanks for sharing. Did you also look at the early data released recently. See below:

"The study was designed specifically to assess the efficacy of tesevatinib in CNS metastases, with full knowledge that these heavily pretreated patients had extensive exposure to other EGFR inhibitors and that tesevatinib therefore may not control peripheral disease well due to the previous development of EGFR inhibitor resistance mechanisms. Thus, as expected, five of the 12 pretreated patients had peripheral disease progression, while in four of those five patients, tesevatinib controlled CNS lesions."

It may not effectively control peripheral cancer.

Kkh

scohn
Dear kkh130.

Dear kkh130.

Here is another clinical trial you might possibly want to look into. It is for patients with Exon 20 mutations in either EGFR (such as the T790M your father has) or HER2, and specifically includes a research arm with patients that have CNS metastases.

The press release on the trial is here:
http://investor.ariad.com/phoenix.zhtml?c=118422&p=irol-newsArticle&ID=2...

The Trial number is NCT02716116, and details can be found here:
https://clinicaltrials.gov/ct2/show/NCT02716116

It is currently being offered in California (Stanford), Colorado (Denver), Massachusetts (Boston), New York, Tennessee (Nashville), and Virginia (Fairfax). This trial is also being considered by my wife depending on the next couple of CT results, so we know it will also be coming sometime soon to Chicago, as my wife's current trial oncologist will be leading it there.

The trial mentioned by kempton is a Phase 2, and a little more focused on the CNS metastases, and this one is more targeted to the more resistant Exon 20 mutations (and is only at Phase 1), so I thought it might give you another possible trial to look at.

Wishing your father and all your family peace and hugs this holiday season,
scohn

Wife, non-smoker, dx 4/24/15 adeno NSCLC stage IV. HER2 Exon 20. 6/15 6x Carbo/Alimta; effective. 9/15 Alimta maint; ineffect. 11/15 - Opdivo; ineffect. 4/16 - ptK7 trial; effective 1.5 yr. 9/17 Gemzar; effective 16 mo. 8/18 -TAK788 Trial; ineffective. 10/18 Abraxane; effective. 7/19 Kadcyla; effective. 10/19 Carbo/Alimta/Keytruda followed by Alimta; ineffective. 4/20-Poziotinib; effective. 7/20-4/21 - Enhertu. 4/21-?? Abraxane/ramucirumab.

kkh130
Thanks scohn. My dad has exon

Thanks scohn. My dad has exon 19 deletion, but I will ask his Stanford oncologist.

kempten
Thank you kkh for making me

Thank you kkh for making me aware of the early data . This is a disappointment of course.
If you learn of any other trials for us exon 19 patients , please let us know.
I hope you will come across a more promising trial.
Best wishes

Kempten

scohn
Hi kkh130.

Hi kkh130.

Good luck checking things out. Let me know how things go.
As for the trial I mentioned, one of the experimental arms is:

Experimental: Expansion Cohort 4
AP32788 treatment for NSCLC patients with other targets against which AP32788 is active (examples include EGFR exon 19 deletions or exon 21 substitutions [with or without T790M mutations] and other uncommon EGFR activating mutations), with or without active, measurable CNS metastases.

So it seems like having an original Exon 19 deletion, along with a subsequent Exon 20 T790M substitution, your Dad might be a good candidate for the trial.

All the best to you and your Dad this holiday season - we'll be thinking of you.

Best, scohn

Wife, non-smoker, dx 4/24/15 adeno NSCLC stage IV. HER2 Exon 20. 6/15 6x Carbo/Alimta; effective. 9/15 Alimta maint; ineffect. 11/15 - Opdivo; ineffect. 4/16 - ptK7 trial; effective 1.5 yr. 9/17 Gemzar; effective 16 mo. 8/18 -TAK788 Trial; ineffective. 10/18 Abraxane; effective. 7/19 Kadcyla; effective. 10/19 Carbo/Alimta/Keytruda followed by Alimta; ineffective. 4/20-Poziotinib; effective. 7/20-4/21 - Enhertu. 4/21-?? Abraxane/ramucirumab.

kkh130
Thanks, scohn. I will take a

Thanks, scohn. I will take a look at this trial. I am taking him to hospital for MRI tonight, hopefully the brain remains stable. I will keep you updated.

Thanks,

Kkh

sbasit01
Hi,

Hi,
My mother has stage 4 NSCLC. She took Traceva for 9 months at the start first line of treatment. The disease progressed after which she underwent 8 sessions of chemo which kept the tumour stable for almost a year.
She was on alimta and carboplatin. It stopped working after which she went through 4 sessions of immunotherapy which showed progression.
We went back to chemotherapy but she had pericardial fluid resulting in pericardial window. She refused to go through further chemotherapy. She also developed brain metastasis due to which she had to undergo cyberknife.
she has now started Tagrisso but is also taking dexamethasone for her brain metastasis. There is severe swelling in her right leg and she is also having dyspnea and fever. The problem is we can't know if she has the T790M mutation because second biopsy came negative for any tumour tissue present. It said the node through which the tissue was taken wasn't big enough to show metastasing tissue. She's gotten to weak to undergo another needle biopsy and plasma biopsy isn't available in my country!
We've taken Tagrisso as a last resort but I'm not sure if this is helping her. she seems to be getting worse.
Please suggest if it's safe to take Tagrisso without the T790M mutation test.
Many thanks
Sameen

JimC
Hi Sameen,

Hi Sameen,

Welcome to GRACE. I am sorry to hear of the progression of your mother's cancer through more than one line of therapy. Tagrisso is known to be effective against lung cancer which has the T790M mutation, but its efficacy is not clear against non-T790M positive disease. It's not that it isn't safe to try it; it certainly can be a more easily tolerated therapy than chemotherapy, it's really just a question of whether it will help her.

If a follow-up scan shows significant progression, then typically her options would be for chemotherapy, since she's already tried immunotherapy and targeted therapy. If she doesn't want to try another chemotherapy option, or if she continues to weaken to the point where her doctor doesn't feel that it is something she can tolerate, then unfortunately you will want to look to palliative therapy to keep her as comfortable as possible. There are times when patients improve as a result of palliative therapy, but in general it's just a good choice to make a patient as comfortable as possible.

My best wishes to you and your mother for comfort.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

sbasit01
Hi JimC!

Hi JimC!

Thank you for getting back so soon and sorry for the late reply. Things have been pretty stressful and we seem to be confused as to what would be best for her. she had been on Tagrisso for a month. She underwent her CT scan last evening and it showed much advanced progression and fluid build up in both the lungs. Her oncologist is saying that she's to weak to undergo chemo at the moment and to continue taking Tagrisso as a month is too little time to determine if the drug is working.
My concern is that she only started getting deep vein thrombosis when she started this drug and if her disease is progressing is their any point in continuing this line of therapy?

Thank you
Sameen

catdander
Hi Sameen,

Hi Sameen,

I'm sorry your mother isn't doing any better. Deep vein thrombosis and pericardial effusions are common symptoms of lung cancer but neither are typical side effects of tagrisso. Your mother's oncologist would need to explain why he/she's keeping your mother on the drug but it's probable the thinking is she will do no worse off the drug, if the drug isn't causing too many side effects. Normally if targisso is going to work you will know in the first 6 weeks. If the side effects are manageable and there's no other treatment options that's reason enough to give the drug a couple more weeks to show itself.

I hope she shows improvement if not in anti cancer treatment in comfort care.

All best,
Janine