Ibrance (Palbociclib)
Comments
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lulubee, I'd written a fairly lengthy post to you last night, but now see I must have lost it when our power went off for a few seconds during a storm. Hope you're doing much better today, and like everyone else here, I am so grateful that you are a very knowledgeable, informed patient with the confidence and presence of mind to advocate for yourself as you did! Your experience is an invaluable lesson to us that not all docs are oncology-savvy, and even with the best of intentions, can inadvertently make bad judgment calls. Hugs & prayers that things continue to look up for you now that the problem has been i.d.'d and so much fluid removed. Please keep us posted!
Shetland, glad you are moving forward. And your comment about continuing to take Letrozole made me smile. Who would have thought we'd get to the point where taking a med w/out our onc's knowledge might be viewed as living wrecklessly or defiantly?! Deanna
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Shetland, I'm with you about the letrozole, I had already decided if I join a trial I'm not going off of it for a month or whatever, 5-6 days should do fine, no? And yes there is fatigue in early months on Ibrance, but that all goes away..
For the trial with gedatolisib, I didn't check but I think that is a dual PI3K and mTOR inhibitor, so would be akin to Afinitor, no? Sorry, there are so many things to check up on, and we can't go around the country consulting everybody- one reason this board is so helpful..
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Shetland - It's amazing how shock can render a type A person like me completely dysfunctional. Yes, break it down. Step by step. You have a lot on your shoulders during this (possible but hopefully not) progression. It has to be dealt with despite the shock. You are doing incredibly well. We're here for you to bounce things off, but in the end we make the multitude of decisions about critical details alone. So take exceptionally good care of yourself....
I do feel better that you are on letrozol. It's an amazing drug and almost certainly helping. Your doctor is grasping for data points to help her make a decision, but the fatigue, as you say, hasn't changed. They don't think about your situation as much as you do, so trust yourself.
I am very concerned about you and think about you often. Please check in and let us know what's going on, even if it's not much.
I tried to line up a second opinion doc last summer but it was a disaster. At least I know SCCA is out. My best guess at the moment is that I would contact the folks on this thread who go to UCSF and UCLA and start speed dialing their doctors for an appointment. The Boston and NY folks also have great doctors, but much farther for me. Options here in New Mexico are pretty thin, so whatever I do will involve a plane flight.
nbnotes - side effects were bad then got better, then bad, then got better, then bad then got better; however, the periods of bad side effects have gotten shorter as learn how to mange them.
teacher - Ibrance received rapid FDA approval so we are all basically in a big distributed clinical trial. However, Pfizer has issued guidelines for managing neutrophil counts and fever caused by neutropenia that are pretty straight forward. Everyone on Ibrance should study the guidelines so you know when to ask for a CBC panel and when to think about dropping your dose. If you study them and follow this thread you will see that they are pretty much universally followed. The more experienced doctors will tweak both the dosing schedule AND the dose based on discussions at conferences or with the clinical trial, and that is not discussed in the the Pfizer guidelines.
I would not assume the infection is caused by ibrance and low neutrophils. In general, people aren't getting more infections on ibrance. But do take extra care of yourself. Stress, fatigue and the lack of exercise that follow all cause us to get sick. The A/I's alone run me down. We need estrogen.
I just finished week 3 of my 12th cycle. A little whipped, but I just spent the weekend sledding with four 10 year olds. My neutrophil count is pretty high and I am starting my week off the stuff. All good.
>Z<
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Cure-ious - Gedatolisib is a dual inhibitor. From the NCI web site.
An agent targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. Upon intravenous administration, gedatolisib inhibits both PI3K and mTOR kinases, which may result in apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K.
I get confused because I thought PI3K was a target in the larger mTOR signaling pathway. In some sense we are talking about the same pathway. However, gedatolisib is definitely attacking two targets. And I hope that Apg's cancer is getting whacked without mercy on all fronts. The problem with trying to find the answers to anything related to cancer is that you just get more questions ... time to go for a run.
>Z<
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Ah, good to know I'm in a nest of rebels like myself!
Ok, after reading the comment from Cure-ious about PI3K and mTor, I poked around the internet and found a site that lists a zillion PI3K drugs. I think this outfit sells chemicals to researchers. Their chart had a column with symbols under C2B, and it seems to indicate five drugs that inhibit it at least partially. I cross referenced these on a site called my cancergenome.org. Viola! Sandpiper and taselisib. The trial site says the trial will be enriched for PI3KCA, so I think that means they take some others as well. It is 2:1 taselisib vs. placebo. If I don't get the drug (assuming I'd be able to make a good guess) or it doesn't work, I am not precluded from using afinitor later. Does this make sense? Caution -- student driver. Now I feel nervous, like when you make an offer on a house and don't know if it will be accepted.
(Gedatosilib had no + in the C2B column.)
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Lwrite, poikilocytosis is included in what those of us in the lab world call "red blood cell morphology" . When you have a CBC drawn, certain criteria would have us make a smear of the blood and look at the cells. I would say that poikilocytosis (cells varying in shape) is most commonly seen in anemia. Usually there are other abnormalities with it such as macro or microcytosis, hypochromia, anisocytosis. The hematocrit and hemoglobin may be low also.(H&H), as well as the total red cell count. There are varying degrees of anemia, of course. If I saw this on my CBC, I would not be alarmed at all. Oncologist might recommend iron or B12,depending on your numbers. My H&H is slightly lower than normal for me on Ibrance, but not abnormal. Your next CBC may not show the "poik" at all. Hope this is helpful. MJH
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Sandpiper is now only open to those with PI3KCA because they have enough others. Shoot.
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Lulubee - you are amazing (and v funny!). We are cheering you on at every step and learning from you too - thank you and rock on!
Question that may be unanswerable and/or uninformed: Would Ibrance do much alone? I ask b/c that's all I've got going as I await stupid runarounds with specialty pharmacies (turns out my insurer deals with one for Ibrance and another for Xeloda, and no one told me things were stalled out). Anyway, with the Faslodex shots stopped I've only got my remaining Ibrance on board - but is it likely to be doing anything?? I'm so nervous, agh.
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Shetland- I wouldn't want to do Sandpiper if I didn't have the PI3KCA mutation, because there is enough in the literature to support the idea that those with the wild-type enzyme will not be strong responders, and in fact I read in one paper that the trial would include some wild-type PI3K patients who do get the drug (taselisib) included as another kind of control group! Like placebo, you don't want that..
But what do we know? The best is to call the people running the trials directly and ask them these questions. I would think gedatolisib would be OK for you, because even if the PI3K does not get blocked, you will still get your mTOR blocked- and that is the same reasoning for Afinitor, just the hope is that gedatolisib will be more effective and/or fewer side effects. If they have a site close enough, you could call to discuss it with their administrator?
Seagan- of course Ibrance is working on its own, it inhibits CDK4/6 and that is why it is not only used in combination with Letrozole or Faslodex, but is being tried in combination with all sorts of other drugs and in various cancers, too. I was just reading today that it kills breast cancer stem cells, which are the most dangerous for metastasis
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I'm beginning to think there is no trial for me. I never have been one to fit standard categories. I checked the details on the gedatolisib trial, and it is for newly diagnosed stage iv/metastatic with no prior therapy. Not me. I really want to do a trial with faslodex plus some kind of mTor drug, so I can save the aromasin + afinitor combo for later. I want to do faslodex because my onc thinks going to another aromatase inhibitor right now is not best, and I agree.
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My onc is looking into a trial with Taxol +/- aurora kinase inhibitor. New to me, and I'm too worn out and addled to look anything up without falling asleep (you could say it's been a rough weekend). She may be having me gurneyed down to diagnostics in a bit to get one of the qualifying bone mets scans.
Anyone know anything?
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MJH, Thank you for the lab information!!
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This sounds like NCT02187991 It is a phase 2 study with two arms: paclitaxel alone and paclitaxel with Alisertib.
"The rationale behind assessing the effectiveness of the addition of alisertib to weekly paclitaxel therapy in patients with Triple Negative Breast Cancer and highly proliferative ER+ and HER2- breast cancer is based on the unmet clinical need for effective strategies to prevent or delay resistance to taxane therapy in the metastatic setting. Synergistic or additive effects have been observed in breast cancer xenograft models which involved alisertib added to either paclitaxel or docetaxel. Alisertib inhibited the Pgp-mediated efflux of paclitaxel in a cell culture model. In addition, Aurora Kinase A is frequently overexpressed in Triple Negative Breast Cancer (TNBC), and expression levels have been shown to be prognostic in both of these breast cancer subtypes. The combination of alisertib with paclitaxel has also been investigated in a Phase 1 study in patients with locally advanced or metastatic ovarian and breast cancers, with preliminary evidence of activity in both tumor types including 6 PRs (partial response) and 3 SD (stable disease) in 11 patients with metastatic breast cancer."
I can say that I found weekly Taxol quite do-able and very effective.
Get some rest if you can, lulubee. We are thinking of you.
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I had read somewhere .. I think it was one of your posts cure-ious ... that they did a trial of ibrance by itself and it did not do much. if so, it needs to be combined with something.
Cure-ious - where are you seeing the ibrance kills stem cells ... will want that in my files.
>Z<
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Thank you so much for the helping hand, Z. I had a feeling I could count on you! It really makes all the difference to have this brilliant community just a keyboard away, especially during frightening times that are loaded with conundrums and too many pain meds.
The current idea is to hit this quickly with IV chemo, one dose per week, and then circle back to Ibrance/exemestane as soon as we can.
When my onc started talking chemo yesterday, I gotta say I felt a wave of sadness over losing my connection to all of you on this thread. I just got here! In ten years, this is the smartest assortment of patients I've yet seen on a BCO thread, and I am really inspired by the lovely support and exploration of information that happens here. So... whew... now that I know I'm headed right back to Ibrance (hopefully soonish), I think I will just stick around through this fling with chemo.
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Please continue to hang out with us! Once a member of the Ibrance Club, always a member:
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Z, this article in Nature late last year found that "blocking expression or kinase activity, using a pharmacological inhibitor [Ibrance], prevented breast cancer stem cell self-renewal."
http://www.nature.com/articles/srep35383
Lulubee, I feel the same way about this amazing group
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Lulubee - The Ibrance thread is like Hotel California, you can check out but you can never leave.
One would think we would be trying to make you laugh, but looks like it will be the other way around.
Jokes aside, I am very concerned that this landed you in the hospital. Please take care and stay close. Hope you have a plan to plow through some good books, catch up on some movies and generally check out of the hospital situation, mentally.
The trial looks great. I hope you get the alisertib but if not, Taxol alone is a well tolerated chemo and tough on cancer.
Hugs, healing thoughts and sweet dreams.
>Z<
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I failed on Ibrance/Faslodex in December, but keep reading this thread because I have learned so much from y'all (yes I'm from the south
). I signed on to the NCI-MATCH clinical study in late December and promised Zarovka I would keep her posted on how that turned out. I thought I would put this info out there for everyone, because I would like your comments on the result of my DNA analysis and the recommended drug. The purpose of the study is to identify mutation(s) and then match that with a drug included in the study that targets that mutation even if the drug is or isn't commonly used for the type of cancer you have.I have two mutations, TP53 and ERBB2 (HER-2). There is a drug in the study for the HER-2 mutation, afatinib - brand name is gilotrif. It is used to fight non-small cell lung cancer that has certain types of abnormal epidermal growth factor receptor (EGFR) genes. My oncologist recommended I give the drug a try after seeing the results of a scan from a week ago that showed that the one round of Doxil had no effect on my tumors and my CA 15-3 almost doubled in a months time, almost 800 now. I have agreed to try the drug, but have had many seconds and third thoughts if this is what I should do.
Here are some of my thoughts and questions:
1. I'm afraid that the drug will have no effect on my cancer and I feel like I don't have time to mess around on something that does not have a track record with breast cancer.
2. Afatinib is potentially toxic to the liver and my tumors are located in my liver. I have no known impairment at this time but my liver enzymes are above the normal levels since Doxil. I know that pretty much anything I try will affect my liver negatively, but with afatinib I will have my liver enzymes checked every two weeks.
3. Is there a treatment out there that is a great option for liver mets? I asked my onc, and he basically said that regardless of location, it's all breast cancer cells.
4. What do y'all know about TP53 and HER
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I failed on Ibrance/Faslodex in December, but keep reading this thread because I have learned so much from y'all (yes I'm from the south
). I signed on to the NCI-MATCH clinical study in late December and promised Zarovka I would keep her posted on how that turned out. I thought I would put this info out there for everyone, because I would like your comments on the result of my DNA analysis and the recommended drug. The purpose of the study is to identify mutation(s) and then match that with a drug included in the study that targets that mutation even if the drug is or isn't commonly used for the type of cancer you have.I have two mutations, TP53 and ERBB2 (HER-2). There is a drug in the study for the HER-2 mutation, afatinib - brand name is gilotrif. It is used to fight non-small cell lung cancer that has certain types of abnormal epidermal growth factor receptor (EGFR) genes. My oncologist recommended I give the drug a try after seeing the results of a scan from a week ago that showed that the one round of Doxil had no effect on my tumors and my CA 15-3 almost doubled in a months time, almost 800 now. I have agreed to try the drug, but have had many seconds and third thoughts if this is what I should do.
Here are some of my thoughts and questions:
1. I'm afraid that the drug will have no effect on my cancer and I feel like I don't have time to mess around on something that does not have a track record with breast cancer.
2. Afatinib is potentially toxic to the liver and my tumors are located in my liver. I have no known impairment at this time but my liver enzymes are above the normal levels since Doxil. I know that pretty much anything I try will affect my liver negatively, but with afatinib I will have my liver enzymes checked every two weeks.
3. Is there a treatment out there that is a great option for liver mets? I asked my onc, and he basically said that regardless of location, it's all breast cancer cells.
4. What do y'all know about TP53 and HER-2 mutations.
Thanks in advance for any and all comments. I'm supposed to start afatinib on Thursday if I don't change my mind.
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Shetland - I'm sorry you're not finding the type of trial you'd like to be on yourself. Meanwhile, you were a speed queen at locating Lulubee's! Yes, I love this group! Thanks, everyone, for the collective info that we all benefit from!
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DeeDee- p53 is one of the most commonly mutated tumor suppressors in cancers of all kind
There was a strong response reported last year for a late-stage breast cancer patient who got a p53 vaccine in combination with Keytruda (immunotherapy). Here is the link:
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Shetland, Definitely Faslodex, and that alone can work for a long time. I would stay on Ibrance, they don't know that the cells are resistant to Ibrance, right? Then to add an mTOR inhibitor, I know there are trials, will go look around..
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OK, here is the first one- this is combining Faslodex with an Ibrance-like Cdk4,6 inhibitor plus either a PI3K-alpha or a all types of -PI3K (pan-Pi3K) inhibitor- this was phase ib/II, but is not recruiting (ie full) at the moment: https://clinicaltrials.gov/ct2/show/NCT02088684
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Shetland- Don't see any other trial that are open, but OK, so just keep an eye out for RapaLink and newer inhibitors, in the meantime go ahead and take whatever your MO recommends for now?
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Oh gosh, I was in a Dilauded stupor when I asked for help with trial info the other day and for some reason I thought it was Z who dug up the info for me.
SO: BELATED THANKS TO YOU, Shetland!!
Fact is, you're all overdosing on awesome.
Looks like I qualified for the trial. Should be randomized tomorrow. Lots of scans happening.
I will probably get my first infusion of Taxol on Thursday. Weird-- ten years in and I'm just now going to The Chair. Just a wee bit scared, I admit.
Sincerely hope I get to check out tomorrow. Hospitals get old fast
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Lulubee - Yup. It was Shetland who found that trial. Very interested in how the alisertib goes, if you get it.
Now we have to get you OUT of the hospital and through a few IV's. Awful pain in the neck, but all doable. We're cheering you the whole way. Let us know ..
And we have to find a trial for Shetland ... would be nice to add some special sauce to faslodex so it last a long long time. Poking around ...
>Z<
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Shetland, I know there are more trials that we have discussed. How about the PASTOR trial, it looks like its private practic MOs in different places, but includes San Francisco, Santa Barbara (are you west coast)? Anyway, this trial is FASLODEX+IBRANCE+AZD2014 (2nd generation mTOR inhibitor). If you took it, you would want to make sure you do not have the mutation in mTOR (maybe 20% do?) that would render you resistant to the drug (RapaLink overcomes that problem, but is not in clinical trials). I think there are other trials, will keep checking
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Here is the link: https://clinicaltrials.gov/ct2/show/NCT02599714
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And a description of AZD2014: https://www.ncbi.nlm.nih.gov/pubmed/26358751
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