Afatinib and Cetuximab after Tarceva resistance - 1248074

apra
Posts:142

Hello everyone,

As I was browsing the Grace archives today I came across this answer that Dr. West had given in answer to a discussion about mutation testing for EGFR.

http://cancergrace.org/forums/index.php?topic=134.0

I know the position is changed now but I was surprised when he said that :)

The quote below also caught my attention:

   3) "Patients with EGFR mutations live longer when they get tarceva.  However, they also live longer without getting tarceva, and the tarceva recipients actually don't do better than EGFR mutations who got a placebo."

I do hope this stand is changed now. Or is it still a fact. I think this post was in 2008.

I would like to know the latest position on the Afatinib Cetuximab trial which was ongoing last year. Whether it has become a standard practice to prescribe these drugs to those who show acquired resistance to

What is the response so far?

Is there any other promising ongoing trail fo he above group of LC patients?

Cancer care especially for Lung Cancer is always evolving. I am so grateful to Cancer Grace and the research doctors for tirelessly working to make Lung Cancer a very treatable disease, in fact even curable in the advanced stages too. Please keep up the good work. THANK YOU

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Reply # - September 16, 2012, 12:44 PM

Dr West
Posts: 4735

My view was based on what was known at that time, and I wrote a post about "Confessions of a Former Clinical Selector" about the results of the IPASS trial that led me to change my views:

http://cancergrace.org/lung/2008/11/03/ipass-mutation-diffs/

I believe it is appropriate to have a different perspective as new information becomes available that changes the equation.

It is very hard to know how someone with an EGFR mutation does without getting an EGFR tyrosine kinase inhibitor (TKI), because even when they are assigned an alternative therapy in a clinical trial, such as chemo instead of the EGFR TKI, they almost always get an opportunity to receive the EGFR TKI later, outside of the trial. The evidence shows that people have the same survival whether they receive the EGFR TKI earlier or later.

To my knowledge, there really isn't any further information available about the afatinib and cetuximab combination. The data that was presented here really hasn't been updated in a public setting, as far as I am aware.

-Dr. West

Reply # - September 16, 2012, 01:18 PM

certain spring
Posts: 762

I think there is as yet no consensus on how to treat acquired resistance. Dr West wrote a good post about this recently:
http://cancergrace.org/lung/2012/08/05/acquired-resistance-faq/
There are lots of trials happening but I don't get the impression that any of them have yet supplied the next-generation drugs we are waiting for.
Hope your husband does well on the Tarceva for a long time to come.

Reply # - September 17, 2012, 10:25 AM

apra
Posts: 142

Dr. West,

Yes, I read about that "confession". You are a great man. Being unable to have new perspective with different information is the bane of the world today.

Is Afatinib and Cetuximab used in your practice for cases of acquired resistance? I have not read the link provided by certain spring yet, but I will go to it immediately. Thank you for your reply.

I think in such a scenario, using traditional chemo as first line therapy would always be better than to start right away on an oral targetted drug as first line therapy, because your options become limited after using Tarceva or Xalkori in such a case. So perhaps FDA's original aproval for use of Tarceva as second or third line therapy was well founded.

Certainspring,

Thanks for your concern and the helpful link. I will read it now.

Reply # - September 17, 2012, 05:58 PM

Dr West
Posts: 4735

Afatinib hasn't been available except as a clinical trial. At this point, it's going to be made available on an "expanded access program" that isn't commercial drug, but the program is meant for the months prior to anticipated FDA approval. I think it will only be for patients with an EGFR mutation.

I should say that after the initial excitement about this regimen, the enthusiasm has waned some. I think it's because the responses were reportedly short-lived, and also the side effect profile has been a challenge for many patients.

The afatinib expanded access program will be available for people who have already been on Iressa (gefitinib) or Tarceva (erlotinib), I understand. However, getting Erbitux (cetuximab) could still be a challenge, since it isn't approved for lung cancer, isn't widely used, and is pretty expensive.

-Dr. West

Reply # - September 17, 2012, 06:00 PM

Dr West
Posts: 4735

Oh, and Certain Spring is exactly right that there isn't any identified best approach to acquired resistance right now, including among lung cancer experts. Trials are still pretty early along and not reported. Most are still being done or even just being planned.

-Dr. West

Reply # - September 17, 2012, 09:11 PM

apra
Posts: 142

A patient who progressed on Tarceva after doing exceptionally well is now on a trial called CO-1686. It is a phase one dosage trial and she says everyone on the trial is doing very well. The phase II is going to begin soon but they want only EGFR positive with T790 mutations. This trial is by the company called Clovis and my friend is at Karmanos Cancer Institute, Detroit.

I do hope some of these trial drugs become available commercially very soon. Right now I think then the protocol would be to go back to traditional chemo doublets, perhaps some doublet which has not been used before.

Thank you Dr. West for your detailed input.

Nini

Reply # - September 18, 2012, 01:08 PM

catdander
Posts:

Nini,
graceabchen wrote on the 4th page of the thread linked to below about the CO-1686, "In my previous list of interesting trials for acquired resistance (AR), I missed one trial recently announced. The drug on trial CO-1686 actually was on Craig’s list posted in this thread. Here is the title plus site: Study to Evaluate Safety, Pharmacokinetics, and Preliminary Efficacy of CO-1686 in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) Non-Small Cell Lung Cancer (NSCLC): http://www.cancer.gov/clinicaltrials/search/view?cdrid=725058&version=H…. Some GRACE discussions of this drug were made at http://cancergrace.org/lung/topic/egfr-acquired-resistance-and-3rd-gene…. CO-1686 is an irreversible TKI, because it sticks to the cancer cell with a covalent bonding (the strongest bond in chemistry terms). The trial is particularly aiming at AR with T790M mutations. AB " http://cancergrace.org/lung/topic/acquired-resistance-to-egfr-tki/page/…

And there is this recent thread, http://cancergrace.org/topic/tarceva-resistance don't miss cs's links they are also good. But I have a good feeling about your husband's run on tarceva. :wink: so you won't need to worry about this for a while.

Reply # - September 19, 2012, 08:12 AM

apra
Posts: 142

Janine,

Hope you had a wonderful holiday away from the Internet world.

Thanks for the threads. Will read each and everyone.

Yes, I also have a strong feeling my husband is going to do very well on Tarceva for a long time. :)

Thanks and God bless

Reply # - September 19, 2012, 09:14 AM

catdander
Posts:

Yes thanks Nini, we had a great time. Could have stayed longer, the geography is so awe inspiring in the desert canyons of Colorado. Plus we had great cooks feeding us everytime we turned around. I've never gained weight on a camping trip before.
You know as long as you ask questions I'll post links :wink:

Reply # - December 20, 2012, 01:58 AM

heartspy
Posts: 37

Hi Apra - was curious to know if there is any udated information from your friend that was involved in the CO-1686 trial. Would appreciate any patient input from that trial, as we are looking hard at this as a possible option for my husband. Thanks!

Reply # - December 21, 2012, 09:54 AM

apra
Posts: 142

Heartspy,

I believe she is still doing well. I met her on Inspire and right now I have forgotten her name. However if you go to Tarceva Divas and Dudes by Marie Zee on Inspire you may get more information about people on this trial because all of them will have been Tarceva Resitant people.

You have not given a signature. You might like to post something more about your journey.

Hope both our husbands will not be needing this for a long time. Take care.

Reply # - December 27, 2012, 02:27 PM

heartspy
Posts: 37

Thank you very much, Apra and Certain Spring. Have spoken with Mass General in Boston ( we live in Florida) we will visit, in early January, for a consult re: CO1686 / others. I am familiar with Inspire and appreciate the link to those specific threads. Remaining hopeful and wishing you comfort and peace.

___________________________________________________________________________________
43 y/o husband- Native American- dx metastatic adenocarcinoma with EGFR+ mutation in 3/2012. 16x palliative radiation @ T7. Started Tarceva 4/2012 @ 150mg then reduced to 100mg due to overwhelming side effects. Was doing well until last CT in 11/2012 showed acquired resistance/ progression. Hoping for medical miracle.

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