Afatinib-Cetuximab Trial Patient Group - 1244782

Jazz, I'm sorry to hear about these side-effects. I totally understand you going back to Afatinib. When my sister stopped it the lung pain started kicking in two days after she did, so she decided to resume it right away instead of waiting a week (to control for side effects).

Like you, I'm also completely confused as to how the new forums are organized. I can see that the 'Updating each other' thread has been closed, as well as Debra's 'New Plan (and I guess the same is true for many other threads). I thought that we could still choose between writing on the 'Updating each other thread' or start individual treads but I guess I was mistaken.

Any idea where we can find these discussions?

Thanks for your help and good luck with the treatment change,

Myriam

Hi Jazz and Myriam, I'm sorry we have to go through this change again. Since I have this official looking title :roll: I've spent a lot of time fishing around in here. I've found (and might find not) that using the big green bar across the top of each page works well for looking at the whole picture. You can double click on "Discussion Forums" and see the whole forum set up or you can click once on it and a drop down menu to a particular forum can be chosen.

I can move this thread if you want to where Craig put his.
Also I started a community thread on the survival/update forum with the intention that anyone can use it.
For what it's worth, I look at the closed forums as file cabinets I can go back to. Sorry, if I'm going to be fine with change I have to find the easiest way to deal.

BTW Jazz, that old scooter avatar you used to use with the girl standing on the foot board reminds me of a pic of me, no not the fact that she's a bomb shell but her pose and the red top. I meant to find it and use it for my avatar but it's on D's computer and just haven't. Do you ride?

You girls rock,
Janine

Jazz, my sister also has terrible side effects from Afatinib (rashes all over her body) and mynocin seems to help but it's not perfect (she took acutane for a little while but it did not seem to work so she stopped it). Unfortunately, my sister is not doing so good. I'm in California right now (in Vista, a small place about 40 min. away from San Diego) and I just received an e-mail from my cousin who told me that my sister had convulsions again. So I phoned my sister and she told me that she had to go to the ER 2 days ago as the convulsions had started again. They gave her 8 mg of decadron to control for this and it did help (she is now taking 4 mg every 4 hours, at least that's what I understood). However, the decadron is not controlling convulsions completely as she told me that tonight her right hand is still moving on its own and she can't use it at all anymore. She's seeing her radiation oncologist tomorrow or Wednesday, not sure.

I hate this horrible disease. She was supposed to come, with her 2 daughters, join us in CA this Saturday but I'm afraid we'll have to play it by ear and see if the convulsions have stopped by then. I was wondering if Dr. Loiselle or Dr. West would have some insight on this i.e. can these convulsions go away or is the problem going to increase? I hate being so far from her when all of this is happening.

Myriam

Thank you for your kindness Jazz. They are, indeed, forecasting hot weather for tomorrow so yes, we're heading for the beach (I think we're going somewhere called Laguna, does this sound familiar?).

Take care,

Myriam

Forum Tip: If you click on the Discussion Forums main nav button, you'll see the entire new forum hierarchy now available. You have to click down into a subject area to see sub-forums, but everything is in one hierarchy now, much like the original GRACE (Archived) forums.

If there's a new category or forum you would like to suggest, we'll certainly consider it.

If you would like to have a link setup from an older forum (in the cancer sub-type areas) to the appropriate new forum here, don't hesitate to ask. :)

Cheers,

-Mark

Hi Jazz,

We're all still learning a bit as we go and trying to find a good balance between organization, access, efficiency and effectiveness for the forums. Constructive feedback is always appreciated. :)

There is a Clinical Trials & Drug Development forum under the Cancer Basics category.

There's also an EGFR Inhibitors forum under the Cancer Treatments / Symptom Management category.

If there's enough call for similar forums but strictly for Lung Cancer, then feel free to make a suggestion in the User Community Comments/Suggestions forum and we'll certainly take it into consideration.

Cheers,

-Mark

Hehe, no worries - I'm often guilty of the same. ;)

Thank you Jazz! By the way, I used to own a 650cc Kawasaki (when I was 19 years old) and enjoyed it very much, although my father and mother were worried to death....

Myriam

Jazz,

My mom is not in the trial anymore. Disease progression was noted after 6th cycle. (We started in Jan, three cycles with bibw2992 and three with the combo treatment). We are seeking chemo treatments now. Main side effects we had during the trail were also paronychia and rash. Rash was managed but paronychia was a big problem for us too after cetuximab was added. Soaking in warm salt water and antibacterial cream helped but were not enough to stop them. The side effects are tough, but worth it if the treatments are working.

Jinz

Jazz, You are the strongest person I know. I didn't have half your side effects and was whining loudly. I don't think the dose reduction caused my progression. The CT scan I had before the two week holiday, then dose reduction indicated that I was already progressing. It was not at the rate to get me kicked out at that point. I still had rash with the reduction but no pain or itching. Too bad it didn't work, it was tolerable at that point.

Hang in there. I hope something out there can help with the side effects.

best,
Ann

I would just like to say once again that all of you who are participating in clinical trials are such an inspiration. I would like to thank you for future cancer patients who will benefit from the results of your bravery. I'm sorry to hear about the difficulties with side effects. Believe me not a single one of you ever sound whiney.

With love and admiration,
Debra

Myriam,

I'm sorry I overlooked your directed question. Situations such as your sisters are so individualized that I really couldn't say what to expect. I think it's very possible that her seizure activity will get under better control with some medication changes, but it's really hard to say anything with confidence when you don't have access to all of the relevant information. In truth, even when we do have good access, we often can't do much more than make our best attempts at effective interventions and then see how well that works.

-Dr. West

Jazz,

You poor thing. I had severe scalp burn/inflammation with 75mg Tarceva and some sun exposure and I used everything - Minocin, Clobetasol, Clindamycin lotion, Derma-Smooth Scalp oil and still it didn't help. My scalp was on fire!! I finally had to stop taking Tarceva for 5 days to let things cool down, and then restarted yesterday at 50mg. I think the severe scalp problem was triggered by sun exposure. I will try to avoid it.

ssflxl

Jazz, thank you for your kind words. You're an inspiration to me too!

Dr. West, thank you for your answer. I understand that with all the traffic on GRACE (and your regular job), it must be hard to follow up some times.

As for my sister, she's doing much better. Her hand is not shaking anymore (so I guess the decadron is working). She's arriving in San Diego tomorrow night with my two nieces so I'm crossing my fingers for an uneventful vacation! It's great that she can come so I'll enjoy my time with her and her girls as much as I can.

Debra it's great to hear from you, and Janine too.

If you ladies could tell me where I can find updates on you I'd be forever grateful. Otherwise, I'm afraid the "Afatinib-Cetuximab trial" thread will become the new 'Updating each other' thread...:)

Take care everyone,

Myriam

Interesting...hadn't heard of that. Are you definitely on the same dose of afatinib? (It's not that the dose was lower when given as a combination, leading to worse rash with a higher dose of the single agent?)

It does sound like a lot to go through. I think you're well in the range of a dose reduction from the sound of it.

-Dr. West

I haven't really used afatinib directly yet, but I strongly suspect that a dose reduction will lead to less intense side effects. I suspect that your experience of worse rash with single agent than with combination is just a quirky one-time thing in the realm of "anything can happen, I guess", rather than expected. That's not really an answer, but sometimes we just see that weird things can happen in individual patients. That's how we confirm that you're special...

-Dr. West

Thanks for the encouraging update. I'm sorry that I don't have real insight here. We should perhaps see if Dr. Quesnelle happens to know anything about this.

-Dr. West

Dear Jazz - Thank goodness thank goodness, is all I can say.
Interesting choice of metaphor by Dr Camidge. I sometimes wonder if we should compile a directory of GRACE metaphors (girl in a bar, terrorists on the loose, whack-a-mole and so on). This reference to sewing adds a whole new dimension.
I would definitely welcome some clarification on the whole afatinib/cetuximab situation. Maybe I have read too much, but I am now confused. Jazz, I have got to the point where I don't understand what you're saying! :(. Must try to keep up. But delighted to hear your news.

FWIW, thread the needle seems so much more fitting for getting a biopsy done than to balancing the benefits and side effects of a treatment.

Best hopes,

Craig in PA

Hi Jazz,

Yes, several groups have reported HER3 upregulation/activity as a mechanism of cetuximab resistance, although most of this work has been done preclinically.

In order to give you a good answer to your question, I am going to go into a bit of biology and split my answer into two posts. The growth factor receptors are complicated little machines with three main parts: a growth factor-binding domain on the outside of the cell, a domain that passes through the cell membrane, and an intracellular domain where all of the activity happens. The part of the EGFR family of receptors found outside of the cell is normally found in a "closed" conformation on the cell surface, much like a tight fist. In order for growth signals to be sent from these receptors, growth factors bind here and force the receptors to "open" like an open hand. Once the receptor is "open" it binds to another one of the EGFR family receptors creating what's called a receptor dimer, a structure with two EGFR family receptors. Think of this as you putting your two hands together as if you are praying. Once this dimerization happens at the cell surface, it brings the intracellular tails of the receptors in close proximity inside the cell where the kinase domain of one receptor will phosphorylate the kinase domain of the other receptor. This receptor phosphorylation then activates other proteins inside the cell and results in cell growth. Antibodies inhibit the receptors by binding to the extracellular closed fist part of the receptor, where kinase inhibitors prevent activation of the receptors inside the cell.

HER3 is a member of the Epidermal Growth Factor Receptor Family, but there is an important distinction between HER3 and the other members of the family: HER3 is called “kinase dead” which means it doesn’t have a functional kinase domain. HER3 is not capable of activating signaling on its own--it can only work by binding to the other members of the EGFR family and becoming activated by them. This is why kinase inhibitors like afatinib will target EGFR and HER2 but not HER3; there is no activity on HER3 for them to inhibit. Further, cetuximab is an antibody that binds outside the cell exclusively to EGFR so it would still permit HER2/HER3 dimer formation. There are a few other complicated biological reasons that HER3 upregulation can cause resistance to cetuximab and afatinib, but hopefully this will give you at least a partial answer to your question.

Antibodies against HER3 that prevent it from dimerizing are currently being developed and could serve as a concomitant therapy with cetuximab. Alternatively, PI3K is generally thought of as the cell survival pathway most activated by HER3, so inhibitors of PI3K are also being developed in the clinic and would be a logical choice with cetuximab.

Hope that helps,

Kelly

Very nice explanation, Dr. Quesnelle. Thank you for the lesson.

I thought of how difficult it is to get a vein ready for IV for my husband when I saw the threading a needle metaphor.
As a mildly active sew'er, there is a balance of trust that you're at the right place to push the thread through and trust it will go. A bit of actual balance is involved to line the needle and thread up. and of course the balance of size of thread to needle eye. Yes I've been accused of being too rational.

Jazz, It's great to know you are moving on towards a more balanced treatment. Congratulations!

Thank you Dr. Quesnelle for the biology lesson.

Janine

Brilliant answer, Dr. Quesnelle. Thank you so much for taking the time to answer so informatively.

-Dr. West

Hi Jazz,

My understanding is that CO-1686 only targets EGFR. The T790M mutation blocks drugs from entereing the kinase domain of EGFR, so drugs like CO-1686 are simply shaped differently so they can enter the kinase domain of EGFR. If resistance is due to upregulation or amplification of c-Met or HER3, you would still need to inhibit those pathways, exatly as in the dacomitinib+crizotinib trial, as you correctly pointed out. This trial is also really promising because HER3 is known to activate many of the same pathways as c-Met and they are known to have a decent amount co-activation, so inhibiting c-Met along with the other members of the EGFR family is a great way to try and reduce HER3 signaling. Keeping in mind, however, that HER3 won't be inhibited directly by dacomitinib since this drug is a kinase inhibitor. I wish you the best of luck in trying to find the trial that's right for you and good luck on Thursday!

Hope that helps,

Kelly

Hoping for an update from Jing soon.

Glad I finally found you all! I was wondering why I hadn't heard from anyone and was especially waiting on news from Jing.

In the meantime, my side effects have been, for lack of a better word, brutal. The peronychias and fungal infections on my fingernails have intensified. Dr. Lacouture applied silver nitrate and prescribed it for daily home application. Forgot to mention there are a few fissures mixed in with the infected parts! For some reason, my feet and toe nails are stable.

A couple of fingers started to improve but a couple worsened so he prescribed Cefadroxil, replacing the low Doxicycline dose (20mg) I was on. I am soaking my fingers in 1:1 vinegar and warm water, and applying topical iodine ointment. After a several days of applying the SN, the wounds were so raw and painful, I decided to take a few days. I am also supposed to be applying PenLac Fungal nail lacquer but the nails are such a mess with everything else going on, I’ve put that on the back burner.

Furthermore, my eyes are constantly itchy and dry, which so making me totally miserable. My ophthalmologist told me to use OTC drops but they haven’t helped. I am seeing him again tomorrow and I am hope he can recommend something else.

Last week before my infusion, the nurse practitioner suggested taking off a half cycle of treatment to let things heal. I will take her up on that if the symptoms don’t improve. Right now my quality of life is pretty dismal. I have my next scan in mid-August and we’ll regroup at that point.

All best,

Casie

Casie, good to hear from you. Really sorry to hear about everything you are dealing with.
On itchy eyes, I had a bad (Tarceva-induced) case of this earlier this year (recorded at tedious length here), with styes and infections:
http://cancergrace.org/cancer-treatments/topic/tarceva-eyes/
They tried to fob me off with OTC treatments, but it was really bothering me so eventually my GP gave me fusidic acid eye drops (sounds alarming but does not hurt), which sorted me out within a week. I suppose the infections were the result of the itchiness and my rubbing my eyes. I tried absolutely everything for the itchiness, from anti-histamines to hydrocorstisone cream. My comradely advice is to *shout* because it was hard to get anyone to take it seriously.
The fingers sound horrible - I know Jazz has been suffering with this and also Myriam's sister. Has anyone sampled the infection to see what kind of bacteria it is? Dr Lacouture in his Q&A says that these are often staph infections (p. 5 of the transcript, below), and I can testify that a course of flucloxicillin for a staph problem in my lung has also had the happy consequence of clearing up the paronychia in my toes. But they're still going to take the nails off :(
http://cancergrace.org/cancer-treatments/files/2011/09/qa-dr-lacouture-…
Dr L mentions Bactroban and Polysporin, neither of which mean anything to me.
I really hope you get a break and things improve. Very best.

I just wanted to say that I hope you can get to some interventions that will leave you feeling better soon. Please do keep us posted.

-Dr. West

Hello everyone,

Although my sister's onc has approved Cetuximab (which means that she'd be on the equivalent of the Afatinib-Cetuximab trial), things are difficult to move along. My sister's onc is away for a few days, which complicates things further...Anyways, from what my sister told me, the pharmaceutical company providing the Cetuximab is not too hot at the idea of giving it for the purpose of treating lung cancer (I believe it is regularly prescribed in other forms of cancer, however, e.g. colon cancer).

So my sister wants to provide them with evidence showing that the Afatinib-Cetuximab combo has some efficacy in controlling lung cancer. I was therefore wondering if you were aware of any recent paper/article that would have discussed the efficacy of this combo?

I already know about the article that Dr. Pennell wrote on GRACE and the update that Dr. West wrote (from Ross Camidge's experience). Is there anything else I'm missing?

Thanks a million for your help,

Myriam

I believe that there is no more information on the combination than was described by Dr. Pennell. To my knowledge, that work hasn't been published.

-Dr. West

Dr. West, thank you for chiming in.

Jazz, thank you so much for this! My sister will be so happy to have some material to send to the pharma co.

Take care,

Myriam

Jazz, this is fantastic news! I'm really happy for you. Let's hope that the combo has some effect for my sister too.

Take care,

Myriam

Myriam,

Reminder from 2011:
"Activity and tolerability of afatinib (BIBW 2992) and cetuximab in NSCLC patients with acquired resistance to erlotinib or gefitinib."
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&… :

"Disease control was observed in all patients enrolled at RP2D (tumor size reduction up to 76%; treatment duration up to 5+ months so far). Confirmed partial responses (PRs) were seen in 8/22 evaluable patients (36%, 95% confidence interval [CI]: 0.17–0.59), including 4/13 (29%) confirmed PRs in T790M+NSCLC."

Best hopes,

Craig

Of course Afatinib-Cetuximab is being used to treat Lung Cancer. It is in Phase III and unfortunately the drug company closed it, but I hear exceptions may be made based on need. I have been on this trial at Yale New Haven Cancer Center and I was trying to transfer to MSKCC. If you go to the hospital websites and look at the clinical trials you will find information.

As an update to my condition, since the side effects were overwhelming for me, a month ago, at the beginning of my 5th cycle, I was put on a two week “hold” so my infections could heal. Twelve days later, (8/12), I had a scan which showed slight progression and a new small lesion. On 8/14, I met with my oncologist and was advised to end the trial and consider other options. Between the signs of progression and the overwhelming side effects, it just wasn’t working for me.

I have mixed feelings about this turn of events. I was miserable on this trial so I feel somewhat relieved, but am obviously frightened by my uncertain future. I hav been feeling so great being off the chemo and since I am taking my daughter to college next week, I am thankful to have the energy. Nevertheless, I immediately started making inquiries into available clinical trials as well as considering regular chemo. And as Myriam said, it is a frustrating time of year because so many oncologists are on vacation. My husband is concerned about a flare up so we are trying to resolve this ASAP.

Jazz, thank you so much for the tip on following up about Jing. I am right on it!