How to treat the patients with acquired resistance to Afatinib? - 1248536

Tue, 10/02/2012 - 00:20
bunnycollie
Posts:

We don't know the status of the egfr/her2 mutation.
How to treat the patients with acquired resistance to Afatinib?
1. Chemo? such as Docetaxel。
2. super her2 TKIs,such as HM781-36B
3.c-Met TKIs, such as XL184,ARQ 197 etc
4.PI3K/Akt drugs,such as Mk2206.

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certain spring
Posts:

Bunnycollie (and may I say I like your dog!), your very helpful and detailed account of your dad's situation is not showing up, annoyingly. I think you might need to fill in the "Forum Signature" box on the Profile page, rather than the "Biographical Information" box. It might be useful in particular for the doctors to know that your father's cancer is squamous, and that he has already had docetaxel, as you record in his bio.
Could I ask, how do you know that that this is a case of acquired resistance? Could it not just be that the afatinib isn't working?
Hope you get some insight here. Best to you and your dad.

catdander
Posts:

Hello bunnycollie, I agree your dog is beautiful.

Is your father on this trial linked to below?
http://www.clinicaltrials.gov/ct2/show/NCT01156545?term=bibw+2992+AND+s…
I hope the lowering of afatinib has helped reduce his side effects and he is able to maintain on the drugs for a long while.
You know your trial drugs. I'm impressed and thankful that your dad is willing to move our understanding forward by testing these drugs.

I will ask a doctor to give input. You should hear back within the day.

Thank you and your dad and best hopes to you both,
Janine
forum moderator

Dr West
Posts:

bunnycollie,

I'm afraid the truest answer is that we don't know. All of the options you mentioned are options to consider, except that he's already been on Taxotere (docetaxel), so going back to that wouldn't make much sense. Perhaps a chemo like Navelbine (vinorelbine), or perhaps a clinical trial drug that you mention, but unfortunately there is no evidence on the planet to provide a real answer to your question. These treatments are really essentially completely untested in people who have been on several prior agents. In general, we tend to not expect much benefit from further chemo in people who have already received several prior lines of standard chemotherapy, unless they have consistently responded to them.

One other option that might be attractive is a clinical trial with an immunotherapy such as anti-PD1 or ipilimumab -- these approaches have appeared to have been particularly encouraging in patients with a squamous NSCLC tumor.

Good luck.

-Dr. West

certain spring
Posts:

Thanks Dr West for reopening the thread. And thanks Janine for the link to the trial.
BunnyCollie, I feel I missed something important - your dad had a complete response to the afatinib/simvastatin after just six weeks? That's very impressive. And it sounds from your profile as though he didn't have the same kind of response to Tarceva - ie the afatinib worked better?
I'd also be interested to hear more about the side-effects. Reading about other people's experiences with afatinib, I had come away with the impression that these were pretty tough.
Please let us know more if you have time. And I hope that the trial combination keeps on working for your father. He's done amazingly well considering that he's already had to cope with gastric cancer. Hopefully by the time things start to go downhill, there will be more knowledge that can help him. Very best.

bunnycollie
Posts:

Thanks Dr West.
Ipilimumab is a revolutionary drug,I am very interested.
Certain spring:
Yes ,the afatinib has had an amazing respons .
As Dr West said, may be more due to HER2 than to EGFR.
http://cancergrace.org/lung/topic/best-treatment-for-her2-mut-pos-metas…
Major side-effects:
severe diarrhea, more than three times in one day, Imodium (loperamide) works.
mild rash .
poor appetite, lost 22lbs in six weeks.
mild stomatitis, VC,VB works.
severe paronychia,got surgery.
20~40mg simvastatin PO.QD is safe.

bunnycollie
Posts:

2012-10-6,start bibw 2992 30mg/ Simvastatin 20mg, 8 days on, 5 days off
2012-12-8,start bibw 2992 30mg/ Simvastatin 10mg, 8 days on, 5 days off
2012-12-20,CT scan,primary tumors cannot be detected, mediastinal lymph node metastasis
reduced 20%(from 2.4cm to 1.9cm),ca 125 65.

catdander
Posts:

bunnycollie, what a beautiful dog. It's so good to hear about your dad's successful CT. I know you all will be celebrating for a happy new year. Thank you so much for letting us know, it's as important that we hear the successful stories as read the statistics.
Janine

Dr West
Posts:

That's really terrific -- thanks for letting us know, and congratulations to him and your family!

And I agree he's a beautiful dog...I'm a dog lover (you might hear my dog, a keeshond, sniffing around in the background on some of the videos I do at my home).

Happy new year! I hope it's filled with more good news you can share with us.

-Dr. West

bunnycollie
Posts:

Still bibw 2992 30mg.
2013-11-14,Chest CT scan,primary tumors cannot be detected, mediastinal lymph node metastasis remains stable.
My dad refuses to do a MRI or a ECT scan, because he feels good.
Many thanks to Dr.West and such a great site.

Jazz
Posts:

Bunny is SO adorable! Thanks for sharing your pics. What personality!

As for the acquired resistance question, the good news is that if/when Dad gets there, hopefully Clovis (CO-1686) will have the trial available in your country (where are you? it's beautiful, wherever you are) and/or AZD9291, and immunotherapy trials.