Treatment after acquired resistance to Tarceva - 1249220

jenns
Posts:4

Hi, Grace Community. I've just officially joined the site, although I've been a frequent reader of the threads here off and on for several years. Thanks to everyone for posting your experiences on here. It's often helpful to read about other people's treatment regimens and experience with side effects, etc. We're trying to decide on next steps for my mom's treatment by next Monday, and I was hoping to get some input from anyone with experience in treatments after acquired resistance to Tarceva (specifically with T790M mutation, if possible). We were hoping to put my mom in an Afatinib/Cetuximab trial, but unfortunately that doesn't seem to be an open option right now. Her oncologist has presented us with the following options: 1) Chemo (Carboplatin, Alimta, and Avastin), 2) Afatinib only, or 3) Adding Avastin to her current dosage of Tarceva. I'm aware that there is no definitive treatment identified for post-acquired-resistance to Tarceva, but wondered if anyone here has experience with any of the three options mentioned above (or the afatinib/cetuximab trial, for that matter)? The afatinib only option doesn't seem very promising for a second line treatment for those who have acquired resistance to Tarceva when you read about it, so it's looking increasingly like chemo is our best option. My mom is understandably concerned about starting chemo since she's been able to maintain a pretty normal lifestyle managing the side effects from Tarceva (dry skin, rash, bad toes, scalp issues, and diarrhea). If anyone out there has some insight to the chemo option and how well it was tolerated, or other options that have worked well post tarceva resistance, we would greatly appreciate it! Thanks in advance.

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Reply # - October 18, 2012, 03:14 PM

Dr West
Posts: 4735

My general approach in a chemo-naive patient is to initiate a chemotherapy-based approach, sometimes with continuation of the EGFR inhibitor if the progression is pretty slow. Of course, it's absolutely true that there is no evidence-based answer to this question. I have had a rare patient who did a little better with the addition of Avastin (bevacizumab) to EGFR inhibitor therapy after progression, but I haven't been very enthused about that approach when there's anything more than rather marginal progression.

-Dr. West

Reply # - October 18, 2012, 03:26 PM

jenns
Posts: 4

Thanks Dr. West for your quick reply. Is the combo of Carboplatin, Alimta, and Avastin pretty standard in your opinion for this line of treatment? I know I've read about others who were simply on Alimta and Avastin, but perhaps that duo was used as a maintenance regimen after having done other rounds of chemo?

Reply # - October 18, 2012, 07:33 PM

JimC
Posts: 2753

Hi Jenn,

Until recently, the "gold standard" of first-line chemo for lung cancer was Carbo/Taxol/Avastin, but in the last couple years for non-squamous cancers Alimta has been substituted for Taxol. The combination you mention was offered to my wife for first-line treatment 4 years ago, although she ended up with just Carbo/Alimta.

JimC

Reply # - October 19, 2012, 01:42 AM

certain spring
Posts: 762

Hallo Jenn. We have masses of info on afatinib/cetuximab - an entire thread in fact, with several heroic GRACE members reporting their experiences. My impression was that it kept people progression-free for rather less time than one might have hoped, at the expense of some fairly rough side effects. Like you I was interested in the concept of afatinib-only, but that too has seemed less promising than it might at first have been:
http://cancergrace.org/forums/index.php?topic=10527.0
http://cancergrace.org/lung/topic/lets-share-the-experience-of-bibw-299…
and a more recent thread with some of Dr West's comments:
http://cancergrace.org/topic/afatinib-and-cetuximab-after-tarceva-resis…
I understand your mother's concern about losing the flexibility of her life on Tarceva. I went in the other direction - chemo first, Tarceva second. I found chemo very hard - yet others here have managed a near-normal existence, even working while on chemo. It seems to be a very personal kind of reaction.
Depending on where you live, there are a lot of trials out there for post-Tarceva resistance, so that might be an option. Knowing your mother has the T790M mutation could be useful in your search.
Dr West also just wrote a post about sorafenib (Nexavar) in people with the EGFR mutation, which made me sit up and take notice:
http://cancergrace.org/lung/2012/10/17/mission-trial-neg-egfr-mutn-pos/
all best to you and your mother

Reply # - October 19, 2012, 11:35 AM

jenns
Posts: 4

Thanks Dr. West, Jim, and Certain Spring for your responses. We appreciate the information! Sorafenib wasn't one I was aware of so I'll have to look into that. Another point to bring up is the possibility of re-starting Tarceva after the chemo treatment (assuming the onc thinks it wise to discontinue Tarceca during the chemo rounds). I've seen a few postings regarding this but wondered if any of you have specific experience in this working?

Reply # - October 19, 2012, 12:31 PM

catdander
Posts:

I wonder if that is the trial Dr. West mentions here being headed by Dr. Horn at Vanderbilt. "Notably, this study doesn’t require patients assigned to chemo alone to subsequently return to EGFR TKI therapy “re-treatment”, but re-treatment is a component of a very similar trial being done in the US and led by Leora Horn from Vanderbilt, except that the EGFR inhibitor is Tarceva (erlotinib) instead of Iressa, and patients assigned to chemo alone at the time of acquired resistance are put back on Tarceva at the time of progression on chemo to see whether patients will benefit from re-treatment and potentially do better than the chemo/EGFR TKI arm because of resensitization to the EGFR TKI after a period off of it:" http://cancergrace.org/lung/2012/06/19/chemo-with-or-without-ongoing-eg…

However, anyone could use this protocol, one is chemo alone after TKI resistance (iressa or tarceva) or add chemo to tarceva (or iressa).

Reply # - October 19, 2012, 01:00 PM

Dr West
Posts: 4735

No, CO-1686 is a separate drug, not the trial by Dr. Horn.

I have "re-challenged" patients with an EGFR inhibitor many months or sometimes years after discontinuing it due to acquired resistance. My experience has been what the very limited data show -- rarely you'll see a significant response, (my best is someone who had progressed on Iressa (gefitinib) after 5.5 years and then went on Tarceva <1 year later, progressing on chemo in between), and it's not uncommon to see mild improvement or stable disease that lasts for a few months. Overall, it is most likely to be of far less benefit the second time around.

-Dr. West

Reply # - October 21, 2012, 06:30 AM

stefano
Posts: 10

I have started Alimta with 100 mg of Tarceva, after having progression on Tarceva 4 months ago.
The plan is to stop Tarceva if the next scan shows improvement( november). Hopefully the Alimta will work for a while , as we wait on the Lucanix trials results. But I probably will go back to Tarceva if I am still waiting in the spring, if necessary.

Keep the spirit,Stefano

Stage 4 NSCLC
Diagnosed 12/09
Tarceva 1/12/12 until now( adding Alimta in Sept)

Reply # - October 21, 2012, 08:37 PM

jenns
Posts: 4

Thanks Dr. West and everyone for the replies. All great info and much appreciated.

Gail - I have read some about the CO 1686 trial (thanks for bringing it up) and have tried finding information on how that's working for trial patients, but haven't come up with anything really. I know there's an ongoing trial right now in the US, but has anyone heard from individuals actually in the trial as to how it's working/side effects/etc? Since my mom has been confirmed to have the T790M mutation as of last week, we'd be particularly interested in how this drug pans out in the near future.

Stefano - Sorry to hear that you've developed resistance to Tarceva, but also glad for you that it worked for quite a while. I've realized by reading many of these threads how lucky we've been that it worked for my mom for nearly 7 years. The best part about all this is that so many new drugs are in the works and any extra time gained on any drug is only a good thing. My mom started Tarceva when it was basically in clinical trials and there was no reassurance that it would work, so now it's just a matter of finding that next big thing...whether it seems like a big thing now or they realize a year from now that it's having amazing results. I look forward to hearing how your addition of Alimta is working for you and hope that it's the answer to your stabilization for the forseeable future. I hadn't heard of Lucanix, so thanks for bringing that up. I will look into that one as well.

Catdander - Thanks for the info on the Dr. Horn trial. That's actually where the idea came from, so thanks for linking to other thread about that. We will hope that the chemo goes well for my mom here whenever she starts it and if we need to look at options past that soon, I'm sure that going back to Tarceva (if it's discontinued at the time of chemo) will be one of our first discussions to have with the Onc.

Reply # - October 22, 2012, 03:05 AM

certain spring
Posts: 762

Actually I already mentioned the Nexavar trial higher up the thread.
Briefing on Lucanix and immunotherapies here:
http://cancergrace.org/lung/2012/06/13/immunotherapy-for-lung-cancer-pa…
http://cancergrace.org/lung/files/2012/06/Brahmer-Immunotherapies-for-L…
I think the reason you can't find information on CO-1686 is that there isn't much yet. We have several GRACE members who are hoping to go on the trial.
You might find this thread of interest - it's a kind of repository for info about TKI resistance:
http://cancergrace.org/lung/topic/acquired-resistance-to-egfr-tki/page/…
http://cancergrace.org/topic/egfr-tki-and-acquired-resistance (new forums)
best to your mum - her survival is amazing and encouraging.

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