Ibrance (Palbociclib)
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eelder - I had a lupron shot for the first time in early august in my butt. no reaction. on the surgery topic, i am curious whether your canceris IDC or ILC?
>Z<
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Shetland, that's interesting about Monday deliveries. I bet that's why my Walgreen's Specialty Pharmacy said they don't do Monday deliveries.
Today is day 5 of my first week on 75mg Ibrance. I feel horrible. Extreme fatigue and a royal headache. Is this normal?
I have a question, too. I've always had completely normal bloodwork. Nothing is ever flagged. When I had my blood drawn last week (before I started Ibrance), my liver enzymes were double the high level. I know some of you ladies have them shoot into the thousands, but mine are always in the normal range. What makes them go up? I have a bone density scan and CT in the beginning of September, so if there is anything, we should see it then. Hopefully I will still be NED and it won't mean anything
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Z... IDC
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This summary of how ibrance with aromatase inhbitors was recently posted in Inspire by Elizabeth a nurse/chemist who is on the protocol. It answers some questions I had about how letrozol and Ibrance work together, why ibrance was initially only approved as a first line treatment, why you don't wait for progression before you take it, etc. Very well written.
Ibrance works to suppress the activity of a 2 similar enzymes (CDK4 and CDK6) that are involved in promoting the first phase in the cell proliferation/reproduction process. Those enzymes are activated a few steps down the reproduction pathway after estrogen binds to the estrogen receptor (ER).
You can prevent triggering the estrogen-CDK4/6 pathway a number of ways...FIRST, by not allowing estrogen to start the cycle:
(1) interfere with the ovarian synthesis of estrogen and thus greatly limiting the amount that is available to bind to the ER on the cancer cells --by using goserelin, lupron or oophrectomy if premenopausal;
(2) reduce the amount of estrogen in post-menopausal women (or male BC patients) by interfering with the conversion of aromatase into estrogen (using one of the AIs: Arimidex/anastrazole, Femara/letrozole and Aromasin/exemestane);
(3) have a non-estrogen molecule bind to the ER (Tamoxifen and other SERMs); or
(4) have a non-estrogen molecule bind to the ER and destroy it (Faslodex/fulvestrant).
SECOND by not allowing the CDK4/6 paths to proceed:
CDK 4/6 are primarily activated via an estrogen-initiated pathway, so it might seem that using Ibrance now while your AI is working is unnecessary, since you have blocked the action of estrogen-----but there are often other less-commonly-used, non-estrogen dependent paths to the CDK4/6 stage that can be recruited into action by the cell, and so it is possible that even when you have adequate estrogen receptor inhibition, the cancer cell can still recruit CDK4/6 to work, and so the reproduction cycle progresses. If the recruitment of these other pathways is not strong, there won't be much cell reproduction that happens, but over time the cell learns how to engage the alternate CDK4/6 pathways and that is when your oncologist says that hormone blockade has failed. The cancer cells have learned how to progress despite not having estrogen initiate the process...At this point Ibrance MIGHT still work if the alternate pathways into the deeper part of the reproduction process still rely on the CDK4/6 paths, but there are other pathways aside from the one that uses CDK4/6 that the cell can recruit as the dominant pathways via mutations. This is what drives disease progression and drug resistance...
If you wait until your cells have evolved to bypass the CDK4/6 route to reproduction, then Ibrance won't work (that's why it's indicated only for ER+ and/or PR+ cancers,since cells that don't use the ER/PR-to-CDK4/6path already use alternate paths; and one of the reasons that it is recommended as early-line therapy for ER/PR+ cancers) Without doing genomic evaluation of each person's cancer, there's no way to know for sure which pathways are favored by metastatic mutations; but typically the ER/PR-to-CDK4/6 path is not mutated early in metastasis, so there's a better likelihood that Ibrance will work early. If you know that you are having good success using ER inhibiting medications, you have the best chance of having Ibrance work for you. Or if it has been a long time since you responded to anti-hormonals and have used a number of different medications in between (that suppressed and interfered with different pathways), it is possible for cells to mutate back into the old ER-mediated pathways. (This is the rationale for trying an old med again after a few years off of it--there's a chance that the cancer cells might have gone back to relying on an old path that worked for it previously, and so the old medication might be effective again.)
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Thanks for that explanation Z. Very helpful!
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Great article, Z. Both my husband and I found that very informative!
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Thank you for the article Z, that helped a ton!!
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(cue the theme from Rocky): I just finished reading this entire thread! (I know, it's a lot, but this is a new drug, and there are a lot of really intelligent informed users here - I didn't want to miss a thing.)
Z, your explanation of the mechanism of Ibrance really helped me to understand it. Luvmyfam, you and I started Ibrance on the same day. I'm also in Oregon (Eugene area). Pretty hot weather we've been having. Glad it's cooled down a bit.
Someone else mentioned the book You Are the Placebo, by Joe Dispenza. I just picked this one up yesterday at a used book sale. I have so many books to read, but this one moved to the front of the queue.
The Faslodex soreness wore off after a couple of days. Next time I'll take the advice and walk around for ten minutes after. Last time I sat on my injection sites for two hours in the shade sipping a margarita. (I'm not sorry!)
No new weird effects yet from the Ibrance after six days. I've always had sensitive, itchy skin, and I had some of that this week. What do you all use as a moisturizer? I'm looking for something hydrating (watery, thin, soaks in well) without parabens or perfumes.
Oh, and I attempted to change my signature, but was unable to find Zometa on the list of treatments, which I'm getting every three months for bones. What category is it under? I didn't see it under targeted, chemo or hormonal. Maybe I just didn't look carefully enough.
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Eve, Wow! That is quite a feat!
Z, Thank you so much for paraphrasing the points in the article. I was especially interested in why we can't wait for progression on an AI before starting Ibrance, and this gave me the answer. So it's all about how the cancer mutates to find other ways around the paths that are blocked. Wish those cancer cells weren't so damned resourceful! One thing that is not addressed here that I have seen others questioning is HER2 status. Is there any reason Ibrance would not work for a HER2+ person providing they are ER/PR+? I confess I don't understand HER2 at all, except from a tx point of view that there are drugs that only work for HER2+ folks. Thank so much for the info.
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Hi, I use eucerin intensive repair rich lotion for very dry skin. It works well for me. Also, Zometa is a bone strengthener. Hope this helps. Good luck on your journey.
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Hi Zarovka,
You and other cancer geeks might be interested in this long Smart Patients conversation about Cancer as a Biological, Ecological and Evolutionary Process. I kicked it off over 2 years ago and it's a great repository of all things related:
https://www.smartpatients.com/conversations/5140-l...
(free registration required)
If you do go to SP, I suggest following the Crossing Disease Boundaries tag since its greatest value is connecting with other patients who want to be smart and proactive in their approaches to cancer. The breast cancer and advanced breast cancer communities aren't very active, but the overall SP group is.
warm, loving hug, Stephanie
PS, I've been a UCSF patient off and on since the mid-90s and appreciate their techie advice, even if it's a daunting system to navigate and easy to get lost in.
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Stephanie, I remember you talking about UCSF before and find it a helpful reminder that no one center will be the ultimate panacea we seek. Using a multi-faceted and integrative approach makes the most sense to me.
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Z, thank you very much for posting the article.
Everyone's cancer is different and how their cells mutate is different. For those who think you can never "add Ibrance later", that's what we did for me and it's working. I wouldn't give up on the idea altogether. My onc agrees with the conventional wisdom that it "shouldn't" work, but it is and we're both grateful.
I do agree that palbo has the best chance of working in concert. It's the whole concept of dual therapy. If you hit two targets at once, it takes a lot longer for the cells to get around both than it does to get around one.
I'm curious -- does anyone know whether ribociclib inhibits CDK4/6 by the same mechanism as palbociclib? Or is it different?
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Pam, I'm sorry I can't recall who or where but someone, maybe Longterm?, posted something about the ribo that stated that it works on a different molecular level, therefore a different mechanism than the palbo. So hopefully if palbo fails someone the ribo will not.
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Pajim - you make a really good point. The summary I posted states the theory of how ibrance works when it was being developed. That drove certain treatment guidelines, like this is a first line treatment, etc. Things are changing and ibrance has become a second line treatment, etc. The thinking is evolving, but that summary has helped me to understand what they originally believed about the mechanism of action and the interaction with letrozol. This, in turn, helps when I am trying to follow the evolution of treatment guidelines or the logic behind some clinical trial.
In fact, they really don't know how these drugs work. There re so many examples to support this. Ribociclib has to be sufficiently different from palbociclib to be patentable. And I believe it blocks CDK 2 and 4 more than 6. However it does have a similar mode of action to palbociclib. It is interfering with the same reproductive pathway. Ribociclib had a fabulous response in a Phase I trial on a heavily pretreated population. (on average >3 lines of treatment).
And why do tumors disappear in some women on this treatment when cancer cells are immortal and all pablociclib does is stop cell reproduction? Every time I understand a little more, I have 10 more questions. But I still try to understand more. Hmmm.
Jobur - the more advanced treatment strategies are all about cornering the cancer with a combination of therapies. When the cancer mutates to evade one line of treatment there is another mode of treatment interfering with the mutation. They study intensely how cancer avoids aromatase inhibitors and that is what drove the development of the kinase inhbitors ribociclib, palbociclib, abemaciclib et. al. there is a whole new line of study about how cancer avoids the letrozol/ibrance combination.
It turns out that elizabeth on Inspire answered your question about using Ibrance to treat HER2+. This awesome response includes a barely comprehensible reference to the esteemed journal Nature, but maybe those with HER2+ will get it since they live it. I'll copy it here ....
As of this point in time, Ibrance is only approved for ER/PR+ Her2- MBC...however, there is some indication that it may be reasonable to use CDK4/6 inhibitors in Her2+ subtypes--perhaps even more so than with the more typical Luminal A cell type, since there is a higher number of Her2+ tumors expressing active/overactive CDK4/6 pathways:
"Amplification of both cyclin D1 and CDK4 is especially high in luminal B (58 % and 25 %, respectively) and HER2-expressing subtypes (38 % and 24 %, respectively), intermediate in luminal A (29 % and 14 %, respectively), and lower in basal-like tumors that tend to also have frequent loss of pRb" see Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.
There are ongoing and soon-to-recruit clinical trials for all of the CDK4/6 drugs (Ibrance/palbociclib as well as Abemacliclib and Ribocliclib) in Her2+ disease:
A super-quick search of clinical trials finds these two, and I'm sure there are more--
A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer (monarcHER)
This study is currently recruiting participants.
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02675231
An Open-Label, Phase Ib/II Clinical Trial Of Cdk 4/6 Inhibitor, Ribociclib (Lee011), In Combination With Trastuzumab Or T-Dm1 For Advanced/Metastatic Her2-Positive Breast Cancer.
Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT026573430 -
NineTwelve, that is quite an accomplishment, reading through this whole thread.
Lol, Stephanie. "Cancer geeks" that's a new one.
Yes, Zarovka, my onc has on more than one occasion said to me, "We really don't know how this works." And she is pretty high up in the profession.
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Zarovka, thank you for posting the Inspire explanation, I think it helps me understand why I need to stay on the Ibrance even if I become NED. I've been thinking I could stop it and just continue the letrozol, wishful thinking I guess. I'm going to print the original article and discuss it with my onc. While I'm not at a major center, I think he is very knowledgeable. I probably won't know till I see him in early October as I appear to be doing so well that I only see him every two months with blood work done in the off month. I'm one week into the 8th round and doing ok, don't feel great but not awful either. I just keep on keeping on. Scans will be in early October.
Faith ( in the future
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Hi Lynne,
I saw that we had the same names and were both from NH. I actually live on the Manchester/Bedford line. Small world!
I was on Faslodex for my first treatment a few years ago. They did say Ibrance was sometimes given with Faslodex too. I did those injections for almost 2 years. I also had been on Femara/letrozole a couple of times too. I had less side effects with the injections, but I just could not do those again (literally a pain in the butt!). I hope they aren't as bad for you!
Good luck!
Lynne
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NineTwelve - I am in Oregon as well (Salem). I just finished my 9th round of Ibrance and am on day 2 of the 7 days off. The lotion I use is by Alba Botanica. Their Very Emollient maximum body lotion. I even use it on my face. It is hypo-allegenic and Paraben, Phthalate, Sodium Lauryl/Laureth Sulfate or Sodium Myreth Sulfate free. If you have a Fred Meyer's near you, they carry it in their natural foods dept. or you can order it on-line. It is available in 16 oz. & 32 oz. pump bottles. Hope this is helpful.
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Howdy, Neighbor! Thanks for the Alba Botanical suggestion. I had forgotten about that one - used to use it, too.
And lissalou, thanks. Eucerin is one of those brands that is easy to find. They make a lotion for itchy skin, too, I think. And someone else suggested apricot kernal oil. Would be nice to smell like apricots.
Got a call from the pharmacy that sent me the Ibrance. The pharmacist asked about any side effects I might be having. I told her about the drippy nose and some minor throat irritation that went away when I followed the advice (on this thread) to swallow the capsule in marshmallow whip. The pharmacist thought I was about to say, "applesauce".
I said, "Oh. That sounds healthier than marshmallow whip."
She said, "Well if you're taking Ibrance, I think you can have a little marshmallow with it." So there you go - from a pharmacist.
Eve
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Thanks, Z! I've been trying for months to figure out if Ibrance works for luminal B, and couldn't find anything about it anywhere.. These boards are so great!
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Regarding Luminal B.... I am luminal b. I have had a very good response to ibrance so far. I'm on my 5th cycle.
I was very upset when I found out that I was Luminal B. Luminal A is slower-growing, more predictable, etc. Luminal B isn't necessarily fast-growing, but it's unpredictable. These types of cancer can "misbehave." My breast tumor was very small at diagnosis. It sort of explained why it had metastasized despite my tumor being small.
ANYWAYS.... I was expressing to my oncologist that being Luminal B worried me. That it was "bad" prognosis-wise. She made me feel better by explaining that Luminal B tends to respond MUCH better to chemo (ibrance or the like). She said that if I were Luminal A she might not have even put me on ibrance (not just her thinking.... others too). Luminal A doesn't put up much of a fight and so chemo doesn't fight back much. Luminal B puts up a bigger fight, and because of this, these types respond much better to chemo. I'm one example, but I have responded very well so far.
So with regards to "does ibrance work for Luminal B?" YES. It does. My oncologist feels it works better for B than A. Generalizations, of course.....
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Thanks for that insight too, eelder! I am just past a year on Ibrance (125mg) & Femara, but hate taking a drug when I don't even know if its working. I did read that Luminal B type cancers are more aggressive, akin to triple-negative, but that they also are responding much more to immunotherapy and drug combinations that include immunotherapy. So, anyway I hope we have good luck as Luminal B is a minority subtype, and we can see which treatments work best!!
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Interesting that you read that about Luminal B. What I've been told is that triple negative is the hardest to treat, followed by HER2+ cancer. Being HER2- is still "preferable" due to the options out there for treatment - 9 currently with two more effective drugs on the way. Within HER2- you are either Luminal A or B. A is slower-growing, but won't respond as well to chemo. B is more unpredictable (my oncologist has said aggressive isn't a term she'd use to describe it), but responds better to treatment.
The immunotherapy concept is something that I feel holds a lot of promise. We are only just beginning to understand how it can help with breast cancer. My oncologist has said, for me, she would suggest immunotherapy down the road when I stop responding to ibrance (which hopefully is years from now). She felt my situation warranted this approach, so perhaps she had my Luminal B status in mind.
Thanks for sharing!
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How does a patient find out if they are Luminal A or B? I was dx'd as ER+, PR+, HER2-.
I just completed my 9th round of Ibrance and get Faslodex injections monthly. My most recent bone scan showed zero active cancer in my bones, but on my CT scan back in April, the area where the tumor is/was is still discernible. My MO is on vacation, so I have to wait to speak with her later.
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Jazzy - Luminal type can be established by a molecular test or your doctor can guess at it based on how aggressive your cancer is (how fast it is dividing, how differentiated it is from normal cells, etc.). More aggressive cancers tend to be Luminal Type B. Less aggressive cancers tend to be Luminal Type A.
The molecular test is technically complex and not universally used in practiced. After reading eelders post I've been re-reading my pathology reports and I see that my biopsies have not been tested. Nor did the pathologist attempt to classify my cancer as luminal type A or B based on clinical measures (what the cancer looks like/how fast it might be dividing.) Based on my pathology report and what I've read about the clinical expression of luminal type B cancer, I have a moderately aggressive cancer that may be luminal type B, but may not.
The people who make these tests write long papers about how useful they are in guiding treatment, but apparently my doctors so far haven't felt that the information would inform their decision. One more question for my new onc when I see her next.
>Z<
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My onc said probably luminal B for me because of the grade 2 and Ki 67 of 15-20%. This is in spite of high ER and high PR. Since the early stage diagnosis was grade 1, I'd like to ask her if she thinks it was luminal A and changed, or if it was always luminal B. And how does this distinction apply to ILC?
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Mine is Luminal B based on ER+/PR-/HER2- and high Ki67. That said, many of the papers about how aggressive luminal B is are concerned with whether or not it will recurr. Regardless through, the luminal B cancers more quickly resist the anti-estrogen AIs, because the lack or low PR is already an indication that the cancer is not strongly estrogen-dependent. But then by the data Z posted, these cancers may be getting a bigger boost from Ibrance, so you can stay on the femara/Ibrance longer. The new PI3K inhibitors in clinical trials should also help, and I think metformin also inhibits PI3K activity, am trying to research about that now, which would push them back towards stronger estrogen-dependence. Eelder, I really like your oncologist's view, about luminal B just being more unpredictable!
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Hi, it's taken me a few days to post. 1- I only have my I phone and it's not as easy to work on. I had Bone and CT scans on Thusrsday. Results showed some new abnormal uptake in lower ribs, SI joint, and skull. CT scan did not pick it up yet. Ct scan showed more scerosis of current mets which is probably from therapy response. That's good news. The bad news is that I have new findings of ill defined hypo dense lesions in the liver highly suspicious for metastastes. MRI scheduled for tomorrow to confirm. I go to Dana Farber, first thing they had me do is to stop treatment. I already was on my week off (I had a hard time with Ibrance) 75 two on Two off and when I got lowered I think that's where my problems may have started. The good news is that my cancer was 18 years out before the bone mets were found and I did well on Let/Ib until my numbers just kept tanking and I had to lower. So I wanted to share what my next step is. My cancer is slow moving. After MRI confirms mets to liver, (too small to measure from CT yet) the panel board at Dana is looking at maybe a trial for me. One of them mentioned was the P1k3 or maybe just faslodex without Ibrance. My MO is out on maternity leave, the one covering her is out on an emergency leave, so I ended up with a MO that has a handful of patients but does mostly research and is part of the tumor board. He's the one that had me stop all meds. That way if a trial is selected I will be eligible to start. Ibrance and let was my first line after stage 4. I got 10 months but only could do the 125 for 5 of it. It's been a battle because of SE. I am staying in the group until I have the next option to share with you all. This MO I saw had a ton of information. One being, that if your original BC was er/pr pos he believes it always is even if it tests otherwise. Maybe that's why faslodex will be my next line. He said there was not enough room on the paper he was writing on to list all the options I have left. I will know more on Wednesday when I see yet another new MO to give me the MRI results So far I have met with 5/16 MO from Dana. Lol.
I also have had very little pain and will be anxious to see what arexSE from meds and what is actually isn't. As in sore scalp and burning pain.
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LM. That's great news that you have lots of options and a break from meds. Hope the SEs disappear. I know it's scary but this new mo sounds very positive and cutting edge.Keep us posted about your new direction.
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