Well, here we are, barring any last minute complications my wife should start the TAK-788 trial next week. She has already had her main blood work and a CT scan. All she needs now is an updated brain MRI and a blood test for magnesium and bilirubin.
The trial oncologist sounded very optimistic, and said they were having good success with the drug so far (as Jim posted with the ASCO results). Main side effects so far have apparently been diarrhea and an acne-like rash (especially for people who spend time in the sun). And no steroids! So hopefully less sleepless nights and a bit less heartburn (although you can't take any acid reducers on this trial, probably worried about effects on drug uptake since it is a pill). It's a small molecule TKI, designed to bind more tightly to the Exon20 mutations than to the normal EGFR or HER2. And apparently the EGFR cohort for the trial is full, but they need more HER2 patients, so my wife is once more plunging in to help science!
So onward we go - treatment line #5. I'll update after next week (for first day of trial my wife has to spend all day at U of C - the drug in the morning and blood draws every hour to measure release of drug into bloodstream).
Reply # - August 9, 2018, 07:23 AM
I'm hopeful that your wife will respond well to tak 788. Let us know when y'all find some names for it.
Reply # - August 9, 2018, 07:59 AM
It's wonderful that your wife has the chance to take part in this trial and I hope you see terrific results!
Reply # - August 15, 2018, 08:48 AM
Sigh...why can't things be uncomplicated....
Trial has started today, all is good, and my wife has taken her first dose of the pills. All is good except...we got a report of the MRI and apparently there are three small suspicious spots on the brain. Since the spots are so small, and my wife is completely asymptomatic, she is still in the trial, and in the "non-CNS involvement" cohort. But, now we wait to see what the MRI looks like in 8 weeks. The good news is that some recent studies suggest TKIs do a fairly reasonable job of treating targeted brain metastases as well, so this drug may deal with those small metastases as well. But at this point we begin to worry what if the TAK 788 works on the lung and liver and not the brain - do we still get to stay in the study if we have to do some radiation on the side?
There is something about "brain" that just feels different - gives you a different kind of shock. But, in reality, it's just one more bump on this ragged road we travel.....
Reply # - August 15, 2018, 12:28 PM
My wife felt a bit better after talking to the trial PA. The PA said the amount of cancer in the brain is extremely low, the trial drug does cross the blood brain barrier, and the results of the drug so far have been extremely encouraging.
Reply # - August 15, 2018, 01:16 PM
There is something about the brain...
Before stereotactic radiosurgery there was little hope of treating brain mets past wbr. And now there are tki's showing efficacy in the brain. I see 2 places for hope, the trialists have the capability to keep your wife on the drug to see if it works in the brain or let your wife take a brake for radiation then return to the trial.
I'm so sorry about the mir results and hope they stay put.
Sending vibes and hugs,
Reply # - August 15, 2018, 01:21 PM
After talking to the PA we are staying on the trial. But I suspect I am going to be very nervous in 8 weeks when it comes time for the new CT and MRI.
Reply # - August 15, 2018, 01:29 PM
of course. I imagine you'll be stressed most of that time. I know too y'all will be taking the moments of joy when they come.
Reply # - August 15, 2018, 06:15 PM
Reply # - August 15, 2018, 07:56 PM
If only current technology would allow you to upload more than just a picture of that beautiful cheesecake!
I'm sorry to hear of the MRI results, but it's great that your wife is able to stay on the trial and that the trial drug has shown evidence of good CNS penetration.
We'll be looking forward to your update in 8 weeks describing a clean follow up MRI.
Reply # - August 18, 2018, 10:58 PM
Well, we won't know how the drug is doing for a while, but the side effects are certainly starting - all manageable so far, but certainly more than Gemzar and different than POSSIBLA.
So for anyone else considering/starting the trial - here is a side effect update for day 4 - more along the lines of the Carbo/Alimta (but without the general 2nd day ache/crash - so I assume it isn't affecting blood cells so much). Off and on diarrhea (no constipation as with POSSIBLA), some lip/mouth sores, and some heartburn. But luckily, like all of the other chemos, my wife has had no nausea at all! And, if other TAK patients are any indication, my wife is likely to start seeing some of the Acne-rash in about a week. Definitely seems like the side-effects are indeed like what I have read for the other TKIs.
However, the previous chemos has prepared us with our arsenal - Imodium/Pepto for digestive issues, numbing cream for lip/mouth, and some TUMS and watching out for spicy foods for heartburn (alas no acid controllers for the trial, as they need to try and standardize uptake, and reduction of stomach acid can affect drug uptake).
One thing we forgot to ask the trial oncologist was why the dosage is set, and not based on body weight (as all the infusion medications were, and my wife is rather petite) and if the dosage can be reduced on a Phase 2 trial if the side effects seem to be limiting at some point. But we will be seeing the oncologist again within the next few weeks, and the PA each week, for those and more questions we may have.
My wife has also noticed that she has to be very careful to swallow the 8 capsules one at a time, each with a lot of water, as the capsule coatings apparently cause the capsules to stick to each other, and they can get caught in your throat if each one doesn't make it all the way down.
But, it certainly reminds me every day how amazingly strong and courageous my wife is!
Reply # - August 19, 2018, 06:53 PM
I hope your wife's side effects continue to all be manageable and she gets a durable response from TAK-788.
For HER2 Exon 20 lung cancer, I am wondering if you have heard of "Ado-Trastuzumab Emtansine for Patients With HER2-Mutant Lung Cancers: Results From a Phase II Basket Trial"
I don't know if this is a different type of treatment modality than you have already tried, but maybe it could give you another option down the road.
Your cheesecake looks yummy!
Reply # - August 19, 2018, 08:43 PM
Thanks onthemark! I hadn't seen that one yet!
I have been keeping my eye on T-DM1 ever since the European HER2 study review showed it to be much more effective than afatanib, with a response rate of about 50%. It basically works much like my wife's first trial drug, although that one targeted PTK7 (an adenocarcinoma target) rather than HER2. The European HER2 study showed the regular EGFR TKIs really weren't that effective against HER2, which is why we will be anxious to see if the trial TKI my wife is on, designed specifically for Exon20 mutations, is (we hope!) a lot better. Since the antibody of T-DM1 targets the normal portion of HER2, it is thought (but not really known) that it might work better against amplified HER2 cancers (where there are a very large number of HER2 receptors on the cancer cells).
I have also mentioned T-DM1 as a future possibility for a friend of ours who has persistent HER2 breast cancer - it a rare form that shows up as a rash rather than any tumors, so the only way to treat it is to remove the affected area of skin and then treat with Herceptin or other anti HER2 drugs, and then just wait until it shows up again. There is a trial using T-DM1 for just that type of cancer, but it is overseas.
Glad you like the cheesecake! My wife loves cheesecake, so I often make one for our anniversary. Here is a lemon one from a couple of years ago.
Reply # - August 20, 2018, 07:13 AM
Oh dear that looks more scrumptious than the first.
I learn so much from the conversations between you two, onthemark and scohn. I wish y'all didn't need to be in the trenches looking for the next best thing though.
Reply # - August 20, 2018, 07:54 AM
Hey janine and scohn,
I personally vote the 1st one, haha...
it reminds me of the cheesecake my mother used to make before she sadly died of concurrent breast and colon cancer at the age of 51. My sister still makes that recipe. Yours looks very similar! It's a bit lighter than the new york style cheesecakes, not too sweet and extremely creamy. Yum!
My mom was the reason I had . a bunch of tests for various cancers after I quit smoking at the age of 52 (she never smoked).
It was a random xray that picked up my lung cancer early so I was able to have surgery. So for me, cheesecake was already very intertwined with cancer and life in general...
Reply # - August 20, 2018, 09:41 AM
Haha, I attribute my baking skills to my mom. Not that I learned from her but that if we wanted desert us kids had to make it, so we baked a lot as kids. She was otherwise busy raising 5 kids and working full time.
Those cheesecakes are so picturesque. What are the yellow balls between the stars of cream. And the threads of lemon zest marbled on top...ohhhh.
Reply # - August 20, 2018, 10:05 AM
Janine, Jim, and onthemark.
Just another quick thank you for, well, just being there. It's a frightening and draining experience dealing with these wretched diseases, and it is so helpful to have others around to listen and help. So, thank you. I'm sure I will be saying that a lot more times.....
And you have all been so nice, I'll give you a nice batch of homemade truffles. Perhaps that's what I'll do when I retire - sell some "Confections for Cancer - Help take a bite out of the disease!".
All the best,
Reply # - August 20, 2018, 10:27 AM
That's a great idea and you already have the hook.
Reply # - August 23, 2018, 11:48 AM
Hi, I am new here and have not posted on sites before but I wanted to do so this time because I think I may be able to give you some good news. My mother in law who has had stage 4 adenocarcinoma Exon 20 since January 2015 started Tak 788 last December. This is her 5th line of treatment as well. Her first scan mid Feb showed a little shrinkage (but not much.) Each of the 3 scans since have been stable! She has all of the side effects that you listed with diarrhea definitely being the worst for her. She has gone on a family vacation, a 10 day road trip and plans to go to Hawaii in November. In December, when she started this trial, we really thought our time with her was coming to an end. She has malignant pleural effusion in both lungs and had the talc procedure in mid November. Her recovery was tough but by her first scan in Feb, she was again able to go places, drive, garden and live alone. Keep good thoughts and try not to worry too much about the first scan. This drug really seems to be helping people and I hope it will be the same for your wife. I have spent a lot of time scouring sites for information on this trial and was never able to find anyone posting about their results. I wanted to make sure you know that their are very successful results out there!! I wish you and your wife the best. Please let me know if you have any questions about our situation as I will do my best to answer.
Reply # - August 23, 2018, 11:56 AM
One more thing I forgot to mention....my mother in law too had issues with these pills as they kept getting stuck in her throat. She now takes them with a clear gelatin that they sell in the drugstore aisle by the pharmacy. I do not know the name but can get it if you need it. It has been extremely helpful for her. You just mix a little of it with water and make a gel and then swallow a spoonful with your pills.
Reply # - August 23, 2018, 02:18 PM
Thanks so much for the info! It is nice to know that there others out there on this same trial! My wife says making sure to take the capsules slowly one at a time has helped a lot for her. I'll let her know about the gelatin (where did you hear about that?). Even better to know that it has kept your Mother-in-law's tumors stable! Hopefully it will work as well for the HER2.
By the way, what were her other 4 prior lines of treatment? Where is your trial location?
The diarrhea has been bad off and on, but the worst has been the mouth sores and swollen/sore lips. The doctor told her they are actually not mouth sores but something else, I think it's more of like mouth acne sores. They prescribed minocycline for her and said if the side effects aren't better next week then they will reduce the dosage. They also gave her a mouth rinse she can use 4 times a day, and said she can rinse with a saline as often as she needs to. My wife is rather petite, and the doctor said that the dosage is initially the same for everyone, so she has the same dose as a 220 pound man, and reducing the dosage isn't a problem, and they have found very good effectiveness even at lower dosages. Now we just have to see if it has any effect on the brain lesions as well.
It hasn't kept her from normal activities, and we are going on a short trip this weekend, and are planning a longer trip to perhaps Vancouver later in the fall/winter.
In fact, she had some metastasis to the hip just before she went on Gemzar, which went away right with the Gemzar. Her hip pain seemed to be flaring up a bit again about 3 weeks after being off Gemzar, but seems have gone again about 2 days after she started on TAK 788.
All the best to you and your mother-in-law for a strong and sustained response!
And I have come up with perfect name for TAK 788: Eicossa (from the Greek for 20) or Excossa (if you want to get the Exon bit in there).
Best regards, scohn
Reply # - August 24, 2018, 08:37 AM
Welcome to GRACE. Congratulations to your mother-in-law on her great response to the trial, and thank you for sharing the information on her experience with the drug. It's extremely helpful to the GRACE community to get a first-hand perspective on a new regimen.
I hope that your mother-in-law's response lasts for a very long time. Thanks again for your post.
Reply # - August 24, 2018, 08:55 AM
The item she uses to help with the pills is called Thick-It and it is a food and beverage thickener but like I said, I purchased it for her one time right in the pharmacy section of CVS. She was taking the pills with yogurt to get them down and when her Dr. heard that, he suggested Thick it as you are not supposed to eat anything with the pills, even a spoonful of yogurt.
Her trial is at Stanford. She has been on 2 standard first line chemos (like Cisplatin) that worked for about 18 months. She then tried the poziotinib clinical trial at UC Davis and it worked for about 6 months, then Gemzar which did not work at all and finally this trial.
She has mets to her scapula, pelvis, femur, adrenal gland and many lymph nodes. She too has never smoked.
I wish your wife success with this trial. Thank you for your good wishes. I like the new name for the trial! It sounds powerful!
Reply # - August 27, 2018, 11:22 AM
Today's update - we went on a nice weekend in Wisconsin, but my wife was not feeling great most of the time. But she did perk up enough Sat. afternoon that we went kayaking!
Friday aft and Sat morning she had a couple of bouts of feeling really dizzy and nauseous, which we realized was due to the Minocycline she was taking - happened both times soon after she took it (they had prescribed it for the mucositis in her mouth). So, she stopped taking the antibiotic and felt much better, but the diarrhea was still taking its toll, and they told her today that she should stop taking the trial drug for a couple days. She has her regular appt on Weds. and I suspect, based on what they said before, that they will be reducing her dosage.
I'll keep you all posted!
Reply # - August 27, 2018, 07:18 PM
I like the idea of a lower dose and I'm sorry she has to suffer these symptoms. We're so lucky to have you early adopters you're so brave, thank you.
I hope the dose reduction rids her of the nasty side effects and the side effects of the drugs to get rid of the side effects, and keeps the cancer at bay for a long long long time.
Don and I used to love canoeing the rivers around here but haven't gone in a while. I guess the places we love most are a bit more treacherous these days, if you get my older woman drift.
Hoping for the best,
Reply # - August 28, 2018, 10:24 AM
Glad you were able to get away for a bit, and at least get in some kayaking. Hope it was a little cooler up in Wisconsin.
As I'm sure you're aware, dose reductions are often necessary to mitigate side effects, without causing any decrease in efficacy.
I hope that's how it goes for your wife, with a durable response to the new therapy.
Reply # - August 29, 2018, 11:36 AM
My wife just got back from meeting with the doctor. Her mouth sores are definitely getting better, her blood tests were fine, but had really low blood pressure due to dehydration from all the diarrhea (which is just now starting to get a little better). So, they would like her to take a couple more days off from the TAK until she is feeling better, and then resume the trial drug at a concentration of 120 mg (down from 160). She was also prescribed a heavier duty medicine for the diarrhea in case she needs it. Between the harsh side effects of the TAK and the bad reaction to the Minocyclin, this last week was really tough for her. So some deep breaths, some relaxation, and onward once more....
Reply # - August 29, 2018, 12:28 PM
Thanks for letting us know scohn. I hope your wife bounces back, rehydrates and all the side effects diminish soon and you both have a long respite from cancer with this promising medication.
In case you missed it, Dr. West tweeted that his centre is also offering a trial of TAK-788. I hope the photo turns out legible!
"Happy to be able to offer this agent in a trial for pts w/ adv NSCLC harboring EGFR exon 20 insertion mut'n or HER2 mut'n at my center now. Eager to have promising, active agent for these folks. Congrats to authors as well. #LCSM #ASCO18H. Jack West, MD added,
Reply # - September 2, 2018, 02:12 PM
OK - one more time! My wife just started at the lower dosage (120 mg) yesterday, and now we see how it goes! A little diarrhea so far, but it started much longer after taking the pills. There's some heartburn too. So, on we go, and we'll see what's what!
Reply # - September 3, 2018, 09:05 AM
Thanks Scohn, I hope the reduction proves helpful.