Need input, KADCYLA or TAS116?
 

I have to change my protocol, between progression and allergy to herceptin. I am trying to decide between a clinical trial for TAS116, and KADCYLA.

TAS116, is an oral anti heat shock protein that has an affinity for HER2+ cancer, and I have an old tumor assay that shows I am a good candidate for a HSP target. The "PRO" is it's oral, local, and they have an opening, it's a phase 1 but they have the dosing figured out, HSP have been around, and they just added space to the trial, so that says the early results are not killing anyone and might be helping. The "CONS" are the side effects; nausea, fatigue, loss of appetite, etc., the list goes on and on. First up on the severe list is a vision problem, which my onc said I focused on and stopped hearing more. I beg to differ. The trial investigator brought it up and risk to VISION is not something I can ignore. The problems are not blindness, and they resolve once the meds are stopped, but, clinical trial and all - there's still RISK! SUPER Hard to predict which would affect me and to what degree.

My onc. thinks I should try the clinical trial, saying Kadcyla is available if I need it, but the trial will be closed soon, it's an opportunity and the trial doc says she thinks it's good, etc. I feel like they are both trying to sell me a car.

I always thought I'd do KADCYLA next, but it is not without side effects, and again, don't know how it would affect me. The PROS are it's KADCYLA and stands a very good chance of working for me!! The CONS are my allergy to herceptin, which will mean pre-meds and a 6-7 hour infusion time for KADCYLA. Plus whatever the drug side effects.

There are no good answers, and I am having a hard time right now. The more pressure and judged I feel (by my doc, family, friends) the more depressed I become. The more I feel like I "should be more grateful" the more sad I feel. Every time I read of someone dying, it triggers grief, fear and anger. I'm a mess for someone who is supposed to be a pro at this game. I need to make a decision and none of it sounds good. At all.

What am I not seeing?!
Feel free to give opinions and advice...

NCT02965885 - clinical trial info, FYI:
Brief Summary:
A First-in-Human (FIH) study of TAS-116 in patients with advanced solid tumors was first initiated in Japan in April 2014 and has been ongoing since then. The study consists of a dose escalation phase and a dose expansion phase. Three dosing regimens of TAS-116, once daily (QD), every other day (QOD) and 5 days on/2 days off regimens in 21-day cycles, are being evaluated. This phase I study is also planned to enrol with advanced solid tumors in UK to confirm the MTD, safety, tolerability, and pharmacokinetics of TAS-116 in a Western patient population in the dose expansion phase. In addition, patients with HER2+ MBC, NSCLC harbouring EGFR mutations (EGFRT790M+) or EGFR mutations (T790M-) will be further evaluated for safety, tolerability and efficacy in 3 separate cohorts at recommended dose of TAS-116 on the 5 days on/2 days off regimen.

Re: Need input, KADCYLA or TAS116?
 

You are a fighter. Thank you for even considering a trial. That takes courage and guts. I am so thankful to all the women who were part of the Herceptin trial many years ago and to all the participants in any trial. I have been lucky to remain NED for 3 years so I don't have any advice other than to say do what you think is best for you. Do not put any stock into other people's opinions. You know yourself better than anyone. Do what is right for you. Whatever you decide, good thoughts and positive energy are coming your way.

Re: Need input, KADCYLA or TAS116?
 

Flori, in a million years I would not attempt to sway you one way or another over treatment. You've been there and done that a number of times and I can only imagine what it is like to agonize over the next treatment.

I well remember you reaching out and spending time talking me down from a ledge when I was first Dx'd with MBC. I remember the countless times you helped me up from the pit of despair when I really thought my life might end. Whenever I get low or feel sorry for myself, I think if you. I imaging your dancing feet, smiling face and your sweet, happy voice. I see your colors and your textures and the beauty that is your art, the beauty that flows from you. I really don't like to think of you in distress, depressed, confused or anything but strong and present because that's the way I see you, Flori, always. You are a trend setter, a long timer, a cheerleader and a friend, my inspiration and my idol.

You will do what you always do, you will weigh the options and make a choice. It will be your choice, the choice that suits you and it will be beautiful because everything about you is beautiful. Feel my hand take yours and squeeze it, gently. Feel my warmth, strength and love as I embrace you. You've got this.

XO T

Re: Need input, KADCYLA or TAS116?
 

SCG

Ill research this TAS116. It will be book knowledge but maybe it will help.
What I really want to see is how effective the drug is in clinical trials.

Paul

Re: Need input, KADCYLA or TAS116?
 

DonnaH thank you for your kind words of support.

MaineRottweilers, Tracy your words snapped me out of the fear fog and got me breathing and thinking again, thank you for expressing so much to me, it means the world to me and helped me feel connected again, thank you from my heart.

Paul, I am so grateful for your informative replies, I cut and paste nearly all into a save file, and often forward to my kids for explanation along with my updates. TAS116 is being presented as an opportunity, with results in 6 weeks. Thats fine and dandy, but side effects
"Llikely, greater than 20%" include nausea, vomiting, diarrhea, decreased appetite, fatigue, and then 8 more line items down--Eye disorders including blurred vision, night blindness, build-up of fluid in the retina of the eye and eye pain". Plus the usual disclaimers of more or less, worse or even death. The eye problems resolve once meds are discontinued.
The protocol is oral, 5 days on, 2 days off then ct scan at end of 6 weeks. There were 20 spot available, HALF for lung and HALF for breast cancer.
AND the dose escalation phase of the trial was initiated in Japan, who continues along with UK to be studied for dose expansion. The sponsor is TAIHO ONCOLOGY INC
Thanks for any input or info you can find. I can't seem to follow a thread or thought. SCG

Re: Need input, KADCYLA or TAS116?
 

Dear Flori,

Just wanted to share my experience with Kadcyla. I've been on it two years now, and have found it to be quite tolerable. However, Herceptin alone, was the easiest drug I've ever been on. I never had to deal with any of the allergic reactions you've had, so my experience with Kadcyla may not even be relevant. My biggest side effect has been some fatigue for about 3 days following my infusion. I also tend to get bloody noses frequently due to lowered platelets, but have never been so low as to withhold treatment. The neuropathy in my hands and feet has gotten worse, and it was already pretty bad from past Taxotere, but I manage to still do things, albeit more clumsily!

Anyway, your Onc may have a good point in that the Kadcyla will still be there for you if the trial drug isn't working.

You and I have been at this for such a long time, I keep thinking holy cow, they've got to come up with something soon.....right?!

Sending you hugs from the other end of the state!
Kim

Re: Need input, KADCYLA or TAS116?
 

Flori

I did some quick research as I know little about shock proteins. Cancer is so complicateds.
These shock proteins are called chaperone proteins and yes they are very necessary for cancer cell survival but getting results by hitting them with drugs is a bit more complicated.

The way to give you as honest an answer as possible is to personalize it. If you were my wife I would urge you to try something else, perhaps Kadycla perhaps an old regimen like CMF (Cytoxan- Methotrexate- Fluorouracil) or even metronomic therapy which is low dose oral Cytoxan (50mg/day) to inhibit angiogenesis.

What I read was not that encouraging. I saw nothin g about breast cancer. There was a Phase-2 study treating GIST a gastric tumour that usually contains a C-Kit oncogene. C-Kit can be hit by Gleevec (imatinib) but tumours become resistant to Gleevec.

I think they gave 160mg TAS-116 for 5 days in a row. I think the median progression free survival was 4 months. There were no regressions but a fairly high percentage of the patients had disease stabilization---for 6 weeks. That isnt too impressive. The side effects were diarrhea, anorexia, fatigue and eye problems that were reversible when the drug was stopped.

There was anotherstudy with non small cell carcinoma of the lung that produced really no results clinically.Theoretically the drug is interesting but clinically?

The drug acts as a radiation sensitizer but is probably too toxic to be used just for this. Ill do more research tommorrow. As I said I just used speed reading to get a basic idea.
Ask your Oncologist why he or she feels it will be valuable. It is possible Ive missed a lot.
Yet you have to remember that Phase 1 clinical studies are legally toxicity studies not clinical studies. The aim is to judge toxicity of the drug at differing doses not clinical effect. Are you sure the study is Phase 1 and not Phase2. Something doesnt add up. Maybe Ill find something tommorrow.

Just remember we are all here for you

Paul

Re: Need input, KADCYLA or TAS116?
 

Its been a long day and my thought process are not up to par. Since you are Her 2 Neu positive I realized when I sat down that CMF probably would nt be that effective. Let me research tomorrow to see if I can find a connection between the use of Tas-116 and Her 2 neu positive breast cancer. If I find anything Ill put it on the board. If anything there should be something in Pub Med.

Re: Need input, KADCYLA or TAS116?
 

Hi Kim,

Since you have been on Kadcyla for so long, has it happened that they have suspended treatment for a few weeks to get platelets up? My wife was on kadcyla in the past, they switched treatments because they would suspend treatment for 2 cycles at a stretch for platelets to come up. The doctor eventually decided, it is not effective to suspend treatment like this and switched.

Thanks in advance.

Re: Need input, KADCYLA or TAS116?
 

SCG

I did a bit more research on TAS-116 and didnt come up with much more. I found the Phase one clinical trial you mentioned in your first post. They are going to try TAS-116 for Her2Nue breast cancer and the non small cell lung carcinoma with the T790 mutation which involves the methionine amino acid molecule replacing a normal Threonine amino acid molecule. I have a slight idea what this means but I wont bore you with it as it is not important in your situation. It is Phase one which means the emphasis is on escalating doses vs toxicity not actual clinical results. You have to trust your gut feelings. Im sorry you are being pressured. If your guts tell you somone is trying to sell you a car you have to listen to them. Talk with your oncologist in depth as to what kind of clinical results she is hoping for. She might have some knowledge through the "grapevine" that hasnt been published yet.

Only 21% of the patients in the GIST Phase 2 study of Tas-116 had vision problems anbd they were not severe and were reversed when the drug was stopped. About 80% of the patients had diahrrea but I imagine this is controlleable with Imodium. Also loss of appetite and wgt loss.

You mentioned Herceptin (Trastuzumab) allergy without going into detail. Weve talked about desensitization procedures before and IGG vs IGE antibody response. There is a desensitization procedure for Herceptin where increasing IV doses of the drug are given every 15 minutes starting with 20 micrograms of the drug and ending with 40 milligrams of the drug. Perhaps this may be of use.

The new and improved lapatanib, Neratanib (Nerlynx) has been FDA approved and perhaps this will be of some value. Diarrhea is the most prominent side effect of Nerlynx.

Hope this helps

Paul

Re: Need input, KADCYLA or TAS116?
 

Hi Supportwife,
I've been fortunate in that my treatments have never been suspended due to low platelets. When my platelets got down to around 100, I started to worry as my doctor said they might withhold treatment if I got down to 90. Fortunately that was the lowest they have gotten so far. After that they came back up and have been pretty steady at around 115-120. I did start taking some papaya leaf powder, but really don't know if that is what made the difference.

Kim

Re: Need input, KADCYLA or TAS116?
 

Hi Flori

Hope you don't mind me joining in!

Don't know very much about TAS116 but have some experience of Kadcyla/immuno phase 2 trial (180 patients worldwide).

Last year I progressed on Xeloda and had to change treatment.

There was little choice available on the NHS/UK - but "I was lucky" (Doctors words) a trial was available that would suit me - Kadcyla & Tecentriq (immuno drug)/ or Placebo. Well it was a no brainer - I wanted Kadcyla and it was only way to get it in my area.
Joined the trial last February and did well on it until recently.

I had no problems on it, felt good, very minor side effects. So much so, I was convinced I was the only one on the placebo with Kadcyla. Still feel good but a few months ago bilirubin went up ( known side effect of Kadcyla). So some cycles missed or delayed.
4 weeks ago trial unblinded as immuno drug not showing any great benefit. Turns out I was on drug! We were asked if we wanted to stay on trial so 3 of us decided to stay.
Well - that didn't last long this week bilirubin still high so I was time-barred from trial.

This was a phase 2 trial. I don't know what it would be like on a phase 1! Have done a phase 3 trial with no problems.

Like you med team promoting it and only a few days to decide. it was a gut reaction for me - had to do it!

i'm sure you will make the best decision for you

Juls

Re: Need input, KADCYLA or TAS116?
 

Gosh, Flori, how do you decide? Paul's information should lend some clarity for you. At least I hope it does! I do respect the information, and value Juls' resignation that at the end of the day it will fall to you and your "gut" to decide.

Ok. Here are my two, probably worthless cents, but I think if I were in your shoes I'd fight for the Kadcyla strickly based upon the better the devil you know philosophy. Perhaps it will go well for you and you will have a long run with it. By the time it ends something else will arrive for you to try. Hope blooms eternal and you do have 2 treatment prospects before you to have hope in.

Flori, I cannot remember or ascertain from your signature; have you ever done TDM1?

Sorry, that was all a bit rambling. Summation: I wish to high heaven I had a crystal ball because then I'd be truly dangerous & would advise you will the utmost confidence! I will lift you up in prayer, my friend. It is not "all we can do;" it is everything we can do and an honor.

Re: Need input, KADCYLA or TAS116?
 

Hi everyone.
Laurel. I think TDM1 was the trial name for Kadcyla, so same thing.

A am actually a little surprised there IS a trial that someone with so many prior treatments can qualify for - but probably because it is a brand new approach for you.

Just sorry that the Herceptin reaction has gotten to the point of having to get away from it. I am wondering if the new subcutaneous version of Herceptin would have the same problem?? Or if it is even available in the LA area yet.

Wish I had more to add. Your spirit has been good with hunches in the past.
I would not like to feel "pushed" by outside forces either!

Re: Need input, KADCYLA or TAS116 or Pyrotinib?!
 

Honestly, could not breathe or think straight until I started talking on here. Paul, yes--I have met with an allergist and do have a desensitization protocol. My onc is fine with me doing Kadcyla/TDM1 OR that TAS116. The TAS trial doc said she was "nervous" about my sensitivity to herceptin. Okay, well, I'm nervous about everything every day. That's how it is with cancer drugs.

The more I sit with the TAS116 info, plus so much online feedback in support of KADCYCLA, it makes the most sense to me to pass on the TAS116. It just doesn't seem "do-able" with such high side effects reported.

As Laurel put it, better to face "the devil you know". Kadcyla is an FDA approved drug that stands an excellent chance of working, and of allowing me to continue with a good QOL for a couple more years or at least this year. The biggest drawback will be the 6+ hour infusion, along with premeds and whatever reaction they all may give me. (Paul, do you think it is possible, on the other hand, that such a slow infusion rate will mitigate side effects since it's my personal belief that infusing slowly helps us greatly and infusing quickly is how you follow the money? Meaning, Herceptin over 30 minutes allows a chair turn a lot faster than Herceptin over 2 hours, or Kadcyla over 6! Hopefully they are not trying to dissuade me for that reason!!)

I have found an interesting ORAL HER2 trial, using Pyrotinib, info pasted at end of this post. I've reached out to the doctor and will see what I get back. It's more similar to tykerb I believe, so not sure if it alone will help, or if I'll have to add in xeloda, which as we all know, is a buzz kill.

Lastly, stumbled across an amazing blog called theStormRiders.org with highlights from San Antonio. The author is also HER2+ so gives a good amount of focus to info on HER2, which is how I found Pyrotinib.

Here's that link: https://thestormriders.org/2018/01/1...17-highlights/

I have one more consult, 2nd opinion, on 1/31 and am hoping he'll have a magic lens on and will see something about my case that makes sense, and will guide me in what to do or not do. I'll update if, when...

With tons of gratitude,
Flori



Pyrotinib
Pyrotinib (HTI-1001) is a novel, irreversible dual EGFR/HER2 tyrosine kinase inhibitor with unique mechanism of action and good oral bioavailability. Dysregulation of HER2 by amplification and overexpression contributes to tumor development, progression , invasion and poor clinical prognosis. For example, such dysregulation occurrs in 10-30% of breast cancers,6% of colorectal cancers,15-25% of gastric cancers ,15-39% oesophageal cancer and 5-19% of epithelial ovarian cancer.

Hengrui Therapeutics, INC (HTI) is conducting a comprehensive development program in US for Pyrotinib for the treatment of patients with HER2 positive solid tumors, including, but not limited to, breast, gastric and colorectal cancers.

A two-part phase I, open label, dose escalation study for Pyrotinib are underway in the US in patients whose disease progressed on prior HER2 targeted therapies. There are also five phase I trials and one phase I/II study being conducted in China.

In early clinical development (Phase I in China), Pyrotinib as a single agent has demonstrated meaningful clinical benefit (increase in ORR and DCR) and is well tolerated in patients with HER2-positive metastatic breast cancer and advanced gastric cancer. These early clinical activities warrant further clinical investigation for pyrotinib’s potential to benefit HER2-positive patients, especially those who are resistant to or experience disease progression on prior target therapies.

Hengrui Therapeutics, INC (HTI) holds global development and commercialization rights of Pyrotinib, except for in the Greater China region.

Information on Pyrotinib clinical studies can be found in clinicaltrials.gov (NCT02500199).

Re: Need input, KADCYLA or TAS116?
 

Flori

Its late so I can only give you a shoot from the hip answer. If you infuse slowly the blood level of the drug will rise more slowly. Side effects are often associated with the blood level. Im guessing but take an oral drug like Benadryl that causes drowsiness. If you take two Benadryl caps at once you will get more drowsy because the blood levels will be higher.

Im not sure if the same idea applies to allergic reactions but it might. Take Penicillin. Most serious anaphylactic reactions have occurred when the drug was injected and the blood levels increased quickly. Oral Penicillin allergic reactions are more often expressed as rashes or hives. If a patient tells a pharmacist he, she is allergic reaction the highest percentages were oral not iv experiences ie rashes. In fact if you study a book on drug interactions there is an interesting one between the anti-Uric acid drug Allopurinol and Amoxicillin. Taken together there can be rashes and the patient is wrongly considered to be allergic to Penicillin.

Oral allergies can be very serious though ie to peanuts etc. Everything is debatable.

Ill do more thorough research tomorrow to see if I can find any more info. Im also going to research that experimental drug pyrotinib.

Glad youve made up your mind and can breathe a bit easier

Paul

Re: Need input, KADCYLA or TAS116?
 

We are all praying for a great outcome and are sending hugs and well wishes your way.

Re: Need input, KADCYLA or TAS116?
 

SCG

did some research and at least with IV iron, the faster you infuse the drug the greater the chance of allergic reactions. I would venture to say this is true of all the drugs but I cant be sure. It seems that Iron reactions are complement driven where most other drugs are IGE driven. Despite this I would guess that slower infusions might decrease the
severity of allergic reactions in general. People are so individual everything is an educated guess.

As far as money goes it rules everything but it is easy to get too cynical. I thought previously that subcutaneous Herceptin was all about avoiding IV apparatus and saving money. This may have some truth but they combine the SC Herceptin with Hyaluronidase and absorption is good. I doubt a six hour infusion costs them that much more than a one hour infusion except if every pt seen at the clinic recieved six hour infusions they would see less patients so I guess money is involved there too. The vast majority of patients recieve one hour infusions.

I researched Pyrotinib. It has been used in China in pts pre-treated with Herceptin with some definite results. The dosage is 400mg daily and the main side effect is diarrhea. Other side effects are nausea, oral ulceration and low white counts. The rate of diarrhea is about 45% the other side effects about 10%. This might prove to be a valuable drug in time

Hope this helps

Paul

Re: Need input, KADCYLA or TAS116?
 

Okay I saw the big kahuna, papa bear of Herceptin and he managed a few words; stay on her2 directed therapy, Kadcyla over any trial. Just because I had a reaction to Herceptin doesn't mean I'll have one to Kadcyla. Signed my copy of The Making of Herceptin, awkward hug, exit stage right...

So, MONDAY I will start KADCYLA. My anxiety has created a faux stroke, can't speak English, or focus, I jump at the slightest noise, this just sucks, back to square one in how scared I feel to do a new drug. But still, I'll do it. Hoping it doesn't feel horrible like chemo, and hoping I don't feel super sick. This time next week I'll know if I survived the 6 hour infusion both physically and emotionally. Phil and everyone thanks for your help in figuring out the next step. Good reminder for me to follow my gut and how much I need the support of this group. xoxo

Re: Need input, KADCYLA or TAS116?
 

Good luck with the Kadcyla! Many have got a long time from this, without too many side-effects. It's my next step, even though I dropped out of the original Marianne trial.
Best wishes.... Pam