after Tagrisso resistance

Portal Forums Lung/Thoracic Cancer EGFR Inhibitors after Tagrisso resistance

This topic contains 16 replies, has 4 voices, and was last updated by  kempten 2 months, 1 week ago.

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August 5, 2017 at 6:57 am  #1291187    

kempten

Hello

I have been absent on this site for a while . I felt good and took a little ” cancer vacation ” by leading a relatively normal life thanks to stereotactic control of mets that showed resistance under Tagrisso therapy
currently on it for 15 months.

A new brain met was discovered in the cerebellum and needs to be zapped soon ( have some light balance issues ).

This brings me back to my old question from Sep 2016 which you guys answered at the time with suggesting chemo after Tagrisso resistance. I agree it can be very effective just not for the brain.
There is the Kadmon trial for Tesevatinib which showed some success in the brain.
Have there been other developments or trials in the meantime since last year?
This question might have been asked several times before and I’m sorry to bug you again but it is difficult to research this site at length without having been an active reader all along.

I was diagnosed in December 2014 with 9 brain mets along with the EGFR pos exon 19 adenocarcinoma
of the lung.
This December I will reach the 3 year survival stage and am desperately trying to delay leptomeningeal
carcinomatosis.

thanks so much for any suggestions

Kempten

August 6, 2017 at 11:36 am  #1291194    
catdander forum moderator
catdander forum moderator

Hey Kempten, So good to see you!

There is heightened promise and even FDA Provisional Approval of carbo/alimta/pembrolizumab (keytruda) as a front line option. I don’t think you’ve had chemo yet so that would apply to you (insurance may need some coxing). Dr. Jonathan W. Goldman wrote the following piece discribing this combo as his “new go-to first-line regimen for non-squamous NSCLC patients without targetable mutations.” http://cancergrace.org/lung/2017/07/25/why-carboplatin-pemetrexed-and-pembrolizumab-has-become-my-new-go-to-regimen-for-first-line-non-squamous-nsclc-treatment/

I’m going to leave it at that for now and we’re get more info in a bit.

Again, so good to see you’re doing well. Congrats on the cancer vaca. :)

Janine

August 6, 2017 at 6:14 pm  #1291198    

kempten

Hi Janine
Happy to hear from you.
I had a nice time in Scotland ( Isle of Skye) and came home discovering that a new little 22mm” mushroom”
had sprouted in my brain in the meantime.

I think the rest of the body is still under control ??? Will find out by Tuesday ( CT scan )
Dr West’s latest article on the Keytruda /Chemo combo was a little critical. He mentioned increased toxicity and
not knowing what is doing what
and the patient population selection might have skewed the results a bit? Did I misunderstand this?

There are some questions weather I’m a good candidate for immununotherapy
I have had Chronic fatigue syndrome for 25 years and they just learned that the disease has a big inflammatory component. 17 cytokines are messed up. Not sure if this is cause or effect. More research is needed.
Also I have a light case of psoriasis and Interstitial cystitis. All Immune system diseases.
I thought along the lines of Tesevatinib the Kadmon trial. Not sure if I would be accepted into any trial with these pre existing conditions ?
There is also the robot assisted trial finder at MD Anderson ( IBM’s Watson) I was wondering if I could utilize that ? But wait : I just read that the project failed ?

https://www.healthnewsreview.org/2017/02/md-anderson-cancer-centers-ibm-watson-project-fails-journalism-related/

Thanks for replying so promptly.
It is the weekend after all

Kempten

August 7, 2017 at 5:54 am  #1291204    
JimC Forum Moderator
JimC Forum Moderator

Hi Kempten,

Glad to hear that you had a good time in Scotland.

I think your interpretations of both issues are correct. Although Dr. West doesn’t think that the combination is a bad choice, at this point he is not convinced that there are sufficient data to justify evan a provisional approval. The history of results of clinical trials of new agents or combinations is littered with instances of improvements in progression free survival, especially when the small trial population is selected from a group expected to do well, only to find that longer follow-up and larger populations show less impressive results.

And though I wish that choosing a clinical trial was as easy as plugging your information into a computer program, it appears that for the time being it will remain a bit more cumbersome than that.

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

August 7, 2017 at 1:48 pm  #1291206    

kempten

Thank you Jim

I will go about it the old fashioned cumbersome route searching for trials. One other problem is that If I immediately zap any newly discovered met I’ll never be able to get a tissue biopsy which is still mandatory for acceptance in any trials I guess.

Kempten

August 8, 2017 at 6:45 am  #1291209    
JimC Forum Moderator
JimC Forum Moderator

Hi Kempten,

If you’re considering the trial of Tesevatinib, the trial listing doesn’t indicate any need for a new biopsy. That’s not surprising, since it’s not addressing any new resistance mutation. Other trials may or may not require a new biopsy, depending on the target of the tested agent, if any. Most trials do require brain mets to be stable, so if there is any indication the met is growing, it will need to be radiated prior to entry.

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

August 8, 2017 at 7:32 am  #1291210    

kempten

Thank you so much for pointing this out Jim

I don’t know why I thought this ? I was under the impression to have read it on their trial inclusion criteria but I don’t see it now. My mistake.

Any input from you guys about the value of this trial?
I think it showed some effectiveness in the brain but not terribly effective in the rest of the body for some patients in our population?

Do you know of any patients participating and giving feedback of their successes/ failures ?

I’m intending to keep this on the back burner for future consideration if I don’t hear of unfavorable reviews .

thanks again
Kempten

August 8, 2017 at 7:44 am  #1291211    

kempten

Tesevatinib trial

inclusion criteria :

Patients may have received osimertinib or rociletinib, or other agents inhibiting the T790M EGFR mutation, but only if they then receive at least 14 days of treatment with erlotinib, afatinib, or gefitinib and have CNS but not peripheral progression

. Target lesions must not have received stereotactic radiotherapy (SRS). ????????
( I was confused by this statement )

Subjects with minimally symptomatic brain metastases may be enrolled without prior radiation therapy to the brain if they do not require immediate surgical or radiation therapy in the opinion of the treating investigator and in the opinion of a radiation therapy or neurosurgical consultant

Just a little confusing for me

Kempten

August 8, 2017 at 4:09 pm  #1291216    
catdander forum moderator
catdander forum moderator

Hi Kempten,

I’m glad Jim joined the conversation. I don’t know why I didn’t mention Dr. West’s view on the subject of combo treatment with keytruda, I knew it was there. Perhaps that’s why I said I’d leave it for now, but I wouldn’t normally do that. Sorry for any confusion or misdirection.

From what I’ve read in several posts during the years from oncs and members is that inclusion/exclusion criteria are somewhat up to the interpretation by the oncologist at that location. Especially if it seems open to interpretation and one is otherwise a good fit.

Keeping in mind the trial wants to know if Tesevatinib reaches the CNS (Brain or LM) when 1st and 2nd gen TKIs didn’t:
It appears the no srs to the brain applies to a brain met or LM that has appeared during treatment with EGFR TKI. You fit that. Your previous srs shouldn’t matter. In another bullet in inclusion they say wbr is ok as long as is was some time back. I’d argue the same applies to previous srs. Yours was some time ago, right?
It looks like they’re saying it’s ok to have had osimertinib or rociletinib as long as one had (or still had) cns mets after going back to 1st/2nd gen tki. Meaning the tki worked systemically but not in CNS.
I’m confused what is meant by peripheral progression and am guessing it means other than CNS but that would mean the wording is weird. I guess they could mean peripheral lung. Lung cancer doesn’t normally progress to peripheral nervous system so that wouldn’t be it.
I think the last one in your post about minimally symptomatic brain mets is talking about whether or not one needs immediate treatment (radiation). Not whether or not you’ve had it in the past. That way they are letting as many people as possible participate as long as one can function long enough to see if Tesevatinib works.

I hope some of this makes sense.
All best,
Janine

August 8, 2017 at 4:21 pm  #1291217    
catdander forum moderator
catdander forum moderator

I wasn’t thinking about you being on tagrisso. If you wanted to join this trial you’d need to go back on tarceva for 2 weeks. That’s a interesting twist to the study. That suggests in just 2 weeks you might have efficacy in the brain. I guess they just want to rule out the possibility of renewed efficacy to tarceva while those who are taking tagrisso aren’t automatically excluded.

Well i’ll be, I just noticed there are 3 inclusion/exclusion sets. One for each cohort.

August 8, 2017 at 5:35 pm  #1291219    

kempten

Thank you Janine

I was wondering the same thing . My T 790M mutation has disappeared during Tagrisso therapy and only my original EGFR exon 19 mutation is still detectable. Can I assume that going back on Tarceva might do the trick?
I also got my CT results of the neck down to pelvis . Very happy. No mets seen anywhere and the lung tumor that was irradiated in Dec/Jan is continuing to shrink nicely.
So we are dealing ( if nothing else is hiding from few ) with a single visible mass in the cerebellum about
22mm from 3mm 3 months ago.

I will see my onc tomorrow to discuss.

Would it make sense to test the theory that Tarceva might be more effective again for me and I should wait with the SRS of the brain lesion to find out . Once the lesion is gone we won’t know for some time ?

Thanks again for your reply .
I treasure your input , always

Kempten

August 9, 2017 at 7:48 pm  #1291225    

wadvocator

kempten,

It is my understanding from talking to oncologist at SCCA that Tagrisso deals with both the orginal EGFR exon 19 mutation and the additional T790 mutation. So Tagrisso should remain effective even if there is no sign of T790 mutation any longer. I don’t know if the insurance is willing to continue to pay for Tagrisso if T790 mutation no longer exist, but they should be willing to pay for Tarceva.

August 9, 2017 at 8:42 pm  #1291226    

kempten

Thank you wadvocator

I have not had any trouble with them paying for the drug yet . But thanks for the tip.
By the way, my Tagrisso UPS delivery with signature did not go so good today.
Opened box and noticed bottle had been tempered with and 28 pills had been stolen . They left me with 2 pills for the rattle sound I guess that one would expect.
Notified all involved parties and waiting for a Fed Ex delivery on Friday.
How to prevent this in the future??

Arrgh

Just read that Tesevatinib has just been approved as new orphan drug for brain mets and Lepto.
Does this mean I can now get it outside of a trial???

thanks again
Kempten

August 9, 2017 at 10:11 pm  #1291227    

kempten

new possible discovery for novel pain therapy

The scientists discovered that EGFR blockers, routinely given to lung cancer patients to inhibit tumour growth, were as potent analgesics as morphine in mouse models of inflammatory and chronic pain.

http://ecancer.org/news/12130-newly-discovered-pathway-for-pain-processing-could-lead-to-new-treatments.php

August 10, 2017 at 2:50 pm  #1291230    
catdander forum moderator
catdander forum moderator

Wow that’s a lot going on. I’m floored to hear about the theft, not surprised just not heard of a personal experience. Someone knew the box had drugs from a specialty drugstore I assume. If they know what they have where’s the market? The price tag on each pill I assume is over a thousand to US insurance companies. Are there individuals who actually pay that price though? I hope the thief is caught. Keep us posted on what steps are taken in the process and good to know you aren’t having extra trouble getting a refill. I doubt any on our onc faculty would have helpful info on how to avoid that but I’ll ask. When Don took tarceva I picked it up at the specialty office because it was just down the street from my work. How about talking to someone, like the insurance adjuster for the specialty drug store about it?

Interesting to hear about egfr tki possibly having an analgesic effect. Don had a lot of pain issues associated with his pancoast tumor and I remember there was a time when he needed less pain relief meds than other times during his treatment. I wonder if that was while he was on tarceva. That would be good news.

I don’t think lung cancer specialists have much hope that returning to tarceva after acquired resistance to tagrisso will have efficacy. However this belief comes from incidental findings, not from real data from a study. I read the inclusion rule to be more of a just in case rule, so not to muddy trial results.

A short video by Dr. Geoffrey R. Oxnard from Dana Farber talks about how much we don’t know about how mutations work by sharing data on the plethora of mutations that are showing up after acquired resistance.
Too I believe I remember him saying the info come from study of blood not tumor tissue.

http://www.targetedonc.com/videos/acquired-resistance-to-osimertinib-in-t790mpositive-nsclc

Keep us posted.
All best,
Janine

August 10, 2017 at 3:28 pm  #1291231    
catdander forum moderator
catdander forum moderator

I believe orphan drug status have already been developed but at some point the testing stopped, someone else picks up the drug and that testing becomes promising, but don’t quote me on that.

From the FDA, “Orphan designation qualifies the sponsor of the drug for various development incentives of the ODA, including tax credits for qualified clinical testing.”

https://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/default.htm

It goes on the say, “The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. Safety and effectiveness of a drug must be established through adequate and well-controlled studies.”

It sounds like the designation is to get already developed drugs to be sponsored for testing but it’s not for patients not in a trial.

August 10, 2017 at 3:44 pm  #1291233    

kempten

thank you Janine

A new delivery for my Tagrisso is scheduled for tomorrow ( Friday ) . They think it was CVS related and not the shipping company. CVS will cover the loss.

I had an appointment with my onc and radiation onc. The plan is to irradiate the new single brain met sometime in the next week or two and then at some point I might try to make my first appointment with Dr Lecia Sequist at Mass General. My new health insurance will now pay for this visit.
My doctors had already asked her for advice a few times during my care, but I would love to see her personally. Interesting was that Dana Farber’s Dr Bruce Johnson and her where of different opinions concerning my care a couple of times . I had favored her approach at the time.

Thanks again for your tips
Kempten

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