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Alpelisib

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  • nkb
    nkb Member Posts: 1,561

    NewGardener- I am sorry to hear of your progression! Seems like you got a long run on this medication - was it Pigray or a new unnamed Pik3ca inhibitor? Your stats look like you had a good run with the afinitor as well. Seems like there is some benefit for going on Abemaciclib after failed Palbo due to its CDK2 activity. I don’t think my MO would go do that either without more studies. It would be great if one of the oral SERDS got approved soon since they are stronger and not shots. I am interested in what you choose and what your liver biopsy shows.

    I’ll be in Toronto later this month for a visit.

  • cure-ious
    cure-ious Member Posts: 2,700

    Heather,

    I'm sorry that you have to switch but a CDK7 inhibitor could have great efficacy, and I would grab it before chemo in a heartbeat, even in phase 1. As you say, the big questions are the side effects. But, in the lab it looks really outstanding for several different MBC subtypes, and especially for cancers that are endocrine and/or CDK4,6 inhibitor-resistant. I am surprised it is available broadly already, and hope that means that the phase 1 trial is working well - what are the characteristics of your cancer?

    I will go find some CDK7 inhibitor info to post- have been waiting for this to move along for a long time!!!

  • newgardener
    newgardener Member Posts: 97

    Hi Nkb -

    I did have a good run for a heavily pretreated person! The drug (GDC-0077) is still just a number as far as I can tell. As I understand it, it is Genentech Roche's second round of a pik3ca inhibitor as they do not seem to have brought taselsib to market.

    I had an oral SERD/SERM bazedoxifene with palbociclib from 2015-2017. I saw that there is a trial in Canada for a new SERD - SAR439859, but not at the centre I go to, but I'm not sure if I'd be excluded.

    While I do get treated in Toronto, I live in Ottawa. But if I start another Phase 1 trial I'll be in Toronto lots.


  • newgardener
    newgardener Member Posts: 97

    Hi Cure-ious - I was hoping you might chime in. I think you are responsible for 99% of the references to CDK7 inhibitors! I would appreciate any information you have.

    The FoundationOne results that I had pre GDC-0077 showed the pik3ca mutation and ESR1. And that's it.



  • cure-ious
    cure-ious Member Posts: 2,700

    Screens to identify which genes are most important for growth of CDK4,6 inhibitor-resistant ER-positive breast cancer cells identified CDK7 and CDK12 as critical drivers.

    https://cancerres.aacrjournals.org/content/79/4_Su...

    So that means if the cancer has grown likely resistant to Ibrance- Femara/Faslodex, that inhibiting CDK7 would be a great idea. It is also important for growth of ESR1 ER-positive cancers.

    One area where the research is being sorted out but is really muddy is that the initial CDK7 inhibitors also significantly cross-inhibited another kinase, CDK12, which also has very strong anti-cancer activity. There are more selective inhibitors and studies with individual kinase knock-outs that are clarifying which kinase regulates which function. One thing that is clear is that CDK12 inhibition also greatly helps T cells infiltrate the tumor and enables immunotherapy to work on cancers that were otherwise considered "cold" or insensitive to drugs like Keytruda.

    So, it would help to know exactly which version of the CDK7 inhibitor drugs under development you would be getting - can you put in a link to your trial?


  • newgardener
    newgardener Member Posts: 97

    It's this trial https://clinicaltrials.gov/ct2/show/NCT03770494 for LY3405105

    The trial description doesn't actually say what kind of drug it is, but the MSKCC site does - https://www.mskcc.org/cancer-care/clinical-trials/19-099

    I've thought about the SY-1365 trial at Dana Farber but it really is expensive for a non-insured Canadian to get care in the U.S. (I did it to receive palbociclib via a trial before it was available in Canada and ouch!).



  • cure-ious
    cure-ious Member Posts: 2,700

    Heather, it looks like Lily got this drug from ICRF in London:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC59859...

    there is selectivity for this compound for CDK7; it can also weakly cross-inhibit CDK2, which would be a bonus for us.They mention THZ1 (a different early CDK7 inhibitor, precursor to SY-1365) to say that it also inhibits CDK12 and therefore might have more side effects than their drug (but also more anti-cancer activity), however they do not explicitly say whether their drug inhibits CDK12 (presumably not).

    The drug works on its own, but like the others also works better with tamoxifen or fulvestrant. So this trial sounds very reasonable, like when they tested Abemaciclib without an AI. Good luck!!!

    PS Don't worry about missing SY-1365, that's an injection- the maker (Syros) indicates they have developed an oral form but its not yet in clinical trials. If the SY drug is also cross-inhibiting CDK12 it might have more side effects

  • cure-ious
    cure-ious Member Posts: 2,700

    Here is an update on the Syros compounds, including their oral CDK7 inhibitor - they say its activity depends on cancers having alterations in the Rb pathway, which are those that are or were sensitive to CDK4,6 inhibitors, making it useful for cancers that have become resistant to the CDK4,6 drugs

    https://d1io3yog0oux5.cloudfront.net/_8c8381136487...

    You can see that their oral CDK7 inhibitor (SY-5609) is very selective and does not inhibit CDK12. They are also working on a CDK12 inhibitor (which does not block CDK7) that should be fantastic for MBC, if it is well tolerated in terms of side effects

  • newgardener
    newgardener Member Posts: 97

    Thanks so much Cure-ious!

  • Pots
    Pots Member Posts: 189

    Hi ladies,

    I’m starting the Phase 2 Bylieve clinical trial today. I acquired the P13KA mutation after finishing Taxol last fall. I’m in the alpelisib Faslodex arm of the trial.

    Any advice on SE is much appreciated

  • GG27
    GG27 Member Posts: 1,308

    pots, I would advise to have everything on hand for SEs. Such as Imodium, anti nausea meds (you will have to ask what the trial will allow) when I was on the trial they didn’t allow very much and certainly not zofran but that may have changed. Also some kind of antihistamine to start early, maybe a couple of days prior to start? There again none of this was available when I was on it but the trial protocols changed. Ask you trial RN what you can take. Good luck!

  • Pots
    Pots Member Posts: 189

    Day 15...I have enough worrying side effects from the alpelisib (itchy skin rash, possible UTI, hurt to pee, cough or swallow, increasing fatigue, worsening cough) that the MO put me on a 2 week hold to see if the side effects resolve. Things turned nasty on Day 13 and kicked me hard. Sigh. So now we wait to see if the Macrobid, Nexium, Claritin, steroid cream...give me relief.

  • cja09
    cja09 Member Posts: 1

    From Vancouver as well.Just started taking Alpelisib (12 days) & side effects include mouth sores ,no taste, aching muscles,& shortness of breath-it is a quick acting drug as I was told it would be-lymph nodes started shrinking @ 3 days in.I had to pay for it out of pocket as BCC won’t cover yet even though approved by Health Canada.

    Are you on a trial or do you have to pay for it as well? The 1st. month cost me $6,300 & I don’t think I’ll continue if I have to pay that much to feel so bad

  • moth
    moth Member Posts: 3,293

    cja09, there's a more active piqray/alpelisib thread here https://community.breastcancer.org/forum/8/topics/...

    I understand it can take time to start working.

    Also come.say hi on the cdns in BC thread https://community.breastcancer.org/forum/55/topics...

    I'm still hoping we can do a 2020 get together somehow for the lower mainland peeps


  • s3k5
    s3k5 Member Posts: 411

    cja09, as Moth mentioned above, there is a Piqray forum that is kind of active. When I started this drug last month, I was able to get a lot of advice from other Piqray users which definitely helped.

    For mouth sores, my doctor has prescribed a 5% Dexamethosone mouth wash to be used 2x/day. Within a day or two my mouth sores disappeared. For taste, I have found some foods better than the others. Muscle aches did get better with time.

    I had severe rashes on my legs and arms after 3 weeks on Piqray. The dermatologist recommended antihistamines (benedryl, allegra) which has helped. There are some side effects that can be managed and some that we just have to deal with! Please reach out to your MO, I am sure the doctor can advise you what to take for the side effects.

    Regarding the cost, you shouldn't be paying so much - that's a lot for a single drug. I think Novartis has payment assistance on their website - have you checked this?

    https://www.hcp.novartis.com/products/piqray/metastatic-breast-cancer/access/

    I think it is at the bottom of this page.

  • Amy-Louise
    Amy-Louise Member Posts: 8

    I will be starting Piqray in 2 days. I've been on faslodex shots for a couple of years. Initial breast cancer started in 2000, 2 lumpectomies, chemo and radiation took care of it. 14 years later I had mets to the liver. That was in 2015 and I've been through so many kinds of treatments and procedures but I'm still here. Recent CT scan showed possible metastatic disease to a lymph node in my upper chest. I had radiation on it and it was fine in the PET/CT scan in September 2020. The radiologist thinks it may be back and to make matters worse my tumor markers went up from 40 to 80 in one month! So it's time for more treatments. I am nervous about the sugar, the rash, the diarrhea (the specialty pharmacy I got the Piqray from also sent imodium with it). Hopefully I won't go bald for the 4th tjme! Happy to find you all who know a lot more about this drug and it's side effects!

  • karpc
    karpc Member Posts: 192

    Hi Amy-Louise

    Can you post this on the following thread? This one has not been active.

    https://community.breastcancer.org/forum/8/topics/...

  • Amy-Louise
    Amy-Louise Member Posts: 8

    good afternoon people! I had first joined this forum when I started Ibrance which after 9 months hadn't worked st all for me. That was after traditional IV chemo, all for metastatic breast cancer that raised ugly head 14 year after my original cancer and treatment. To say I was totally upset is an understatement!

    I was referred to moffit after the Ibrance didn't work and got all kinds of procedures there. The mets were to my liver and while the tumor(s) responded well to the procedures, the would always come back, more procedures. Finally after a year of no new tumors Moffitt "graduated" me. Everything's been good until a CT scan picked up a malignant lymph node in my upper chest which I got radiation on. At that point I had been getting faslodex shots for a couple of years. Now they are seeing progression and my tumor markers have been going up in big chunks so I am now on Piqray, it's my 11th day and the side effects just keep on coming. I have nausea and vomiting, the rash came today, diarrhea, high sugar, headache. I'm sure some of you have similar issues and I'm wondering if you could tell me how long these side effects last or any other advice you can give me.

    I guess we all will be getting the 3rd vaccine for the Covid, couldn't come soon enough for me!

  • karpc
    karpc Member Posts: 192

    Hi Amy. This page has not been active for a long time. Try this link for a more active forum for Piqray. https://community.breastcancer.org/forum/8/topics/...

    However, that forum is not very active. I am sorry you are having bad side effects. I wonder if you could reduce the dosage. I have been on Piqray for 6 weeks and I have been lucky so far with minimal side effects. My blood sugar is staying low and my stomach has remained fairly calm. My main side effects are a headache and I need to sleep a little longer each night. I started to get a rash on my face the first week when I was in the sun lots but it went away. I do take claritin every morning. Some recommend taking an allergen twice a day. I eat a very low carb diet with no sugar so I wonder if that has helped keep my blood sugar low? I hope your symptoms are settling down. ~Kar