Ibrance (Palbociclib)
Comments
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Jaycee- I am enjoying the discussion about dropping the doseage of Ibrance because, as you say, I've been to chicken to move off of the original dose. And although I was encouraged by all the comments about the MOs apparent confidence that Ibrance is just as effective at the 100mg dose, I have since talked myself out of the idea of considering a lower dose. I ASSUME that these doses have not been directly compared against each other, and that the results of the clinical trials showing that Ibrance doubles the response time to Femara come from the combined results of patients on the trial who were taking anywhere from 75mg-125mg for varying amounts of time. So although MOs are confident that 100mg or 75 mg is just as effective, I doubt now that they base that on any actual numbers, more likely that they have seen patients go for long periods of time on the lower doses. But with no actual statistics to be sure about that point. So long as my symptoms are mostly just about the neutrophil count, I will stick with the 125.
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And, to play devil's advocate, the ongoing trials could in fact show that 100mg or 75mg is actually preferable to 125mg in terms of delaying the time to progression!! More drug is not necessarily better. But without data, I won't bother changing. I'm a lot more concerned with keeping track of whatever options might be called for when I have to change treatment after progression. Plus if the cancer moves to liver and looks aggressive, then there will be fewer options and different trials to consider...
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Cure-ious, my mets were on the liver and bones de nova and Ibrance has been my first attack. Interesting, does your onc not think it will work on the liver? My onc is checking to see if I have the PIK3CA mutation and can go on a trial of alpelisib when I progress. I won't know for another month whether I qualify. I have also not progressed yet. We are hoping I won't need it.
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Cure-ious, I agree that the current data is probably based on the patients on different doses dumped together. It just seems like Pfizer would have at least some data on each of the doses and for some reason are sitting on it. Wouldn't the trial researchers have kept track of dose reductions and the outcome measures of those reductions? It baffles me. I'm going to try and use some of my resources in the research community to find out, if I can. Also, I am asking my new MO. Also, when my specialty pharmacy calls to set up next shipment, they always ask if I want to talk to a nurse. I always say no. I think they used to ask if I wanted to communicate somehow with the drug company. Is that just wishful thinking? I'm asking next time they call.
You're right. There is no data showing the lower doses are as good. There is also no data showing that 125 mg is better.
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Cure-ious. There is a clinical traial at the Cross Cancer Instute in Edmonton Alberta Canada comparing various dosages of Ibrance. The null hypothesis is that lower does will be more effective due to fewer dose interruptions. The PI is Dr Anil Joy. Pfizer prices Ibrance at a 28 day cycle regardless of dosage. I know several Canadian oncologists who say that 50% or more of their patients require one or more dose reductions. I am down to 75 and feel much better
Jo
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Just my ordinary mind thinking there must be some confidence that lower doses may be effective since there is a trial with MUCH lower doses at MD Anderson. One-fifth of the 125mg, if I remember correctly! Yes, it has a companion drug, one they hope will keep the cells from starting to resist the Ibrance.
After my remarkable response to 100mg Ibrance it will be interesting to see if the response remains good on my present 75mg. If not, it will also be interesting to see if my oncologist wants me to go back to 100mg or if we consider moving on to something different. Wouldn't it be great if Ibrance Dancers could all go to 25mg one day? I'm a believer!
Have a Happy Sunday! from PatGMc
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Here's a poster from MD Anderson that was presented at SABCS 2017 that shows the progression-free survival (PFS) for patients that needed dose reductions or dose-delays compared to those that didn't. These are not clinical trial patients, but patients that were treated at MD Anderson.
It looks like the patients that had their dose reduced or had to delay dosing fared slightly better than the ones that didn't. The authors do caution that this could be due to the slightly different patient characteristics in the two groups, but it is certainly encouraging that dose reductions do not seem to adversely effect results. You can see the full size poster here http://sabcs17.posterview.com/nosl/?searchterm=palbociclib&searchtype=PosterTitle (just select to continue as a guest, and the poster is closer to the end of the results).
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Hi, my two cents on the lower dosage. My doc started me at 100mg. I was extremely fatigued and needed to stop in the first cycle due to low numbers. I also learned that I was on an antidepressant that had an interaction with Ibrance increasing it's effects. Pfizer recommended a lower dosage while on the med so we dropped to 75mg. It took awhile, but I slowly transitioned off the antidepressant but my doc said she wanted to keep me at 75mg as I was doing very well. I recently had a 2nd opinion at Dana Farber and the doc was also in agreement with me remaining at 75 mg. I am on my 29th or 30th cycle and am NEAD. I do have fatigue ( but also on 3 blood pressure meds so that could be contributing to the fatigue) but it is manageable. I can get tired late afternoon and can not run like I would like to with my 12 year old daughter but overall my quality of life is pretty good and I am very grateful for this.
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Welcome, NMJanet. I'm glad to hear Ibrance is tolerable and hope it's good to you for a long, long time.
IntoLight, I've seen many women with liver mets on Ibrance on these boards. It's a great first line treatment. It's when someone advances to liver mets while on it that means it is no longer working.
Singlemom, I always love hearing stories of 30+ cycles, and NEAD to boot - how wonderful!
I'm following the dose conversations closely. Have scans at end of month and will be having (another) conversation with MO about it then. Last time we talked she jedi mind tricked me into staying on the 125mg, but will support whatever I decide. PatG, I love and second your wish for 25mg for our younger sisters!
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singlemom - so awesome you’ve been NEAD for that many cycles! Yay! Curious - which antidepressant were you on that conflicted? I am on 37.5 Effexor.
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singlemom, I'm so happy you're doing well! I say extra prayers for all of you who are raising children during this battle with MBC. I look back on so many friends who fought to be here for their children. Catherine, whose son was two and is now through college and married. Judy, whose sone was two and has finished college and got his dream job at Microsoft. Luane, who adopted her daughter as an infant and now celebrates Rachel's Junior year in high school. There are so many more but you get my drift. All of them have been out of treatment with no disease for years! Then there's Julie, who was pregnant when her BC metastasized. The daughter who was eight is a mother and a successful attorney. The baby she was carrying is a Sophomore at the University of Texas. Julie has been in and out of treatment all these years and is in it right now....happy as a clam! And I saw my friend Shirley at the doctor's office Wednesday. She progressed on Ibrance but has started Halaven (sp?) and is tolerating it well. She's 20 years out from MBC!
That is the dose of hope I take every day in addition to the hopeful stories you tell here. My cancer metastasized in March of 2012. Here I am making art and watching my 14 year old granddaughter grow up. God is good.
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Interesting data! Ibrance is such a blockbuster drug, it makes sense they will do many trials to check out different dose regimens and that new combos will definitely use less drug to avoid the dose interruptions if possible. Also, it is possible that if we all live 10+ years, some late-appearing side effects could appear and that reveal that those on the lower dose were much better off- think about lymphedema risks from too much chemo, etc...
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Dang, Pat- good job!! Life is sweet!!!!!
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What I am also missing with respect to the discussion of Ibrance dosing is a correlation of dosage to body weight. I am rather overweight, therefore it might be possible that I either need the higher dosage or am able to tolerate it better than more slender persons. I have not yet seen a statistics on that.
Additionally, I am wondering, whether dose reduction should be considered in case of a complete response as a maintanance therapy.
I am currently in cycle 7 and only had to delay restart once by 1 week after a cycle where I had to take 7+10 days of antibiotics. I appear to have very good response to Ibrance, because my primary tumour (I am de novo stage 4 and had no surgery) decreased in size from 80x25x20 mm to 9x4x4 mm within 6 cycles. I hope that Ibrance and my immune system (I strongly believe that I am one of the patients where Ibrance enables the immune system to see the tumour again as published in this Nature publication from may 2017, because my lump and axillary nodes keep on itching/slightly hurting on and off which I think is due to immune response) are able to basically completely eliminate my primary lump. And why shouldn't the same apply to my bone mets then, which just cannot be seen by CT (just the holes in the bone which will require years to heal). I know that there will always be some cells left which will eventually cause progression some day, but why not dream about being NED?
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Oh, and one more thought on the dosing: here in Germany, people keep saying that who does not have SEs on Ibrance will also not have an effect on Ibrance. If this is true, this would certainly explain why people with dose reductions and dose delays have a longer PFS on Ibrance, simply because they show better response.
I myself have several SEs on my mucuous tissues in my whole body. My ANC after 1 week off is always around 1.3, which allows me to move on, but which is not even close to a normal count. My MO told me that he has people with ANC above 3 after the week off, when we had a discussion whether I may restart without blood testing during the week I will be on skiing vacation (he will not let me).
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Singlemom, that is fantastic on both the NEAD and the 30 cycles. May you have many, many more years of NEAD and see your daughter through all the milestones you have ever hoped for.
Pat, thank you for sharing those amazing stories and congratulations of your eight years living with this beast. You are such an uplifting presence on these boards, always ready to give hope and encouragement.
Netta, those are great results from Ibrance! I hope NEAD is somewhere in your very near future and once it comes it's there to stay. I don't know if it's true that the lack of side effects means lack of efficacy. Significant side effects might mean that you're above a certain concentration, and thus have plenty of drug on board to to its job, but lack of them doesn't necessarily mean that you're not getting enough drug -might just mean your body is better at coping with that concentration.
A difference in body weight could definitely account for some of the differences in tolerability, but so could a difference in CYP3A4 activity (this is the liver enzyme that is mostly responsible for metabolizing palbociclib). There are big differences between individuals, and there are also population differences, even between populations that we might think of as relatively similar, such as North Americans and Europeans. I was looking at the long term follow-up data from Pfizer (also in a poster at SABCS 2017) and it seemed that the European patients needed fewer dose reductions than North American patients. That's probably not explainable by body weight alone.
I would take the totality of the data to mean that if 125mg is tolerable for an individual, there's no reason to lower the dose, but if the side effects of 125 are too much, there's also no reason to fear going down to 100 or 75, until the side effects become tolerable.
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Great points Netta and Piggy! I am not petite either, and ANCs hover right around 1 every time, last time were 0.7. Sometimes I skip a day or two..
Netta, there's a story on onclive (" Taking a new look at primary resection in distant metastatic breast cancer" http://www.onclive.com/specialty/breast-cancer) discussing the question of whether to remove the original tumor, as it could continue to be a source of cancer stem cells and send signals to suppress the immune system. Ongoing trials are looking at this question, and with better drugs and people living longer, they say the recommendations might change to favor of removal of the original tumor. But something worth considering is a preclinical study in Australia showing that the reaction from immunotherapy drugs in particular is much stronger if the primary tumor remains, and they speculate that it gives the immune system lots of cancer cells to prime on, So maybe tumor removal right after some treatment combo that includes immunotherapy? Its a discussion to keep an eye on..
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And good point that you might already be having an immunotherapy reaction from the Ibrance- there is a trial with Abemaciclib and Keytruda, we are waiting for updates anytime, very early 4 month data indicated it was maybe doubling the response to Abemaciclib alone, and if that holds out it would be the first indication that that ER-positive MBC can respond to immuno if presented in combination with CDK4,6 inhibitor. But why does the trial not include Faslodex?! Arrgh...
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Cure-ious: Thanks for your input on the sugery topic. I am not sure how to proceed wrt the primary lump, as there are contradictory results available if surgery is beneficial or not. I know about a retrospective study from the Netherlands which indicates better OS after surgery, but they are not sure, if the women who were eligible for surgery were not the ones with the better prognosis anyway, that being the reason why they underwent surgery. On the other hand, there is a study from India which says that surgery correlates with decreased OS. I believe, there is also a study from Turkey, but I do not remember its result. My MO prefers not to do surgery, because the size of the primary tumor is a very good indicator if the current treatment is working. Additionally, it is measurable disease, which would allow me to access clinical studies, where my bone mets only would not qualify me for. Additionally, I somehow have in mind that inflammation after surgery might trigger tumor stem cell activity causing them to awake from their sleeping status. Very difficult decision indeed... -> Edit: I should have read your link first (it did not work so I had to google it separately): basically all of the studies I mentioned are also quoted in your link! Sorry for posting redundant information.
And I would love to do a clinical study with a CDK 4/6 inhibitor plus Keytruda, but unfortunately, there is none available in Germany. We also did not get this great approval of Keytruda for all types of solid cancers like the FDA lately granted, which would allow any doctor to prescribe Keytruda for breast cancer. I do believe, this would indeed be great for me.
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BTW: sorry for posting so much today, but I got those UTI-like symptoms again (feels like UTI but not caused by bacteria but the Ibrance causing inflammation of the tissue there) and it helps best to tuck myself in the bed under a warm blanket and drink several litres of herbal tea ... while reading on my tablet.
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Good question Cure-pious. I want to know the answer to.💞
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Netta, don't worry about posting too much. I love it when the board is so active. And from your posts, I can tell your English, which was very good to begin with, is rapidly improving. No one reading your posts would ever think English was not your first language. I have a German brother-in-law who has been living in the US for 40 years and his English is no where near as good as yours. Bravo. And it makes us here in the US feel really silly for not teaching our kids multiple languages.
And my UTI-type symptoms, I'm pretty sure, are from the letrozole. Vaginal dryness in the extreme. I use different vaginal moisturizers and it works pretty well. Still experimenting. There is a thread on UTIs with lots of ideas and discussion.
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jaycee49: Thank you. But I must say that I am not the standard German person. I stayed in the US for 1 year as an high school exchange student plus 1 semester in the UK as university student plus 3 months in the US during my PhD thesis. I am a scientist and used to read scientific articles published in English. And I communicate with colleagues from work (France, India) in English. However, I still struggle with language details, e.g. prepositions, and it is much more exhausting than German to me. And German persons are quite straight forward and sometimes lack diplomacy and smalltalking capabilities. So still far from perfect ... not to speak about my accent :-) .
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Netta, I knew you were a scientist- cannot hide that you clearly get the literature!! What area is your PhD? Are you currently working?
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Netta - My family and I lived in Bonn from 2009-2013. While I don't speak German, I learned enough to get by. English was standard in my workplace, however, so i got very used to hearing German- English. There are a few elements of your sentence structure in English that bring back wonderful memories of our time there, so I knew immediately you were German. Where are you located? We all miss it so much and have been back to visit twice since 2013.
Tschuess
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Cure-ious: We will always recognize each other because of the same way of approaching topics. I am a chemist and have been working in pharmaceutical industry for 14 years. Did not prevent me from getting de novo stage 4 mbc. Bad luck to have the lump where it is not palpable, I was at the annual check-up 3 months before dx. Currently, I am not working, but I am planning to go to rehab and restart working afterwards. It feels arkward not to work. Hopefully, I will be stable for some years and able to work at least part-time and enjoy life with my kids (5 and 7 years).
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Hopefully we came at a game-changer time for treatments. Working is key for sanity, plus you may find some contacts in pharma that can give you some insight of what is working or not among the various new drugs. I think working and having as normal a life as possible is very important. I'm glad I didn't tell people at my work nor most of our friends. Just want my normal life! A friend of mine in Berlin died of ovarian cancer when her son was just five, and she only got two years after recurrence, so obviously things can be much worse- hopefully we get a long time, and with good quality of life. It sounds like you are doing exceptionally well for being at such an early stage and with young kids!! One thing that calmed me down was being able to read the literature, and to realize all the exciting stuff that is in development or in trials! Glad you decided to join the boards here!!
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LaurenH and Janky...I don't know whether my rash is the same as yours but I've had red sort of blotches and a rash on the insteps of my feet since I started on Ibrance more than a year ago. It doesn't bother me, it's not itchy but it looks awful. It's there all the time and reduces somewhat during the break but not completely.
Sleep....! I've been taking Temazepam since my first visit to the oncologist when I was only sleeping about 1 to 2 hours a night and was a complete zombie. He told me to take a Temazepam every night and not to worry about it as sleep is so important for recovery. I don't like taking it because I was always under the impression they stopped working after a few weeks but they don't. I also thought they were addictive but I can stop and start any time but when I take them I fall asleep as soon as my head hits the pillow but my problem is early waking. I wake up every hour to have a wee (another story) and get back to sleep but once it's 3 or 4am...ding! An alarm goes off in my head. I don't need an alarm clock or my phone to wake me. That's it. My brain says 4 hours' sleep is more than enough but I beg to differ because I'm tired all the time. Just one more hour and I'd be happy. I've actually backed some inventors who are manufacturing a sleep device called Thim that you wear on your finger. Apparently it wakes you every half hour for the first few nights which is supposed to teach you how to get back to get back to sleep and stay asleep. I decided sleep was worth giving it a try as it's just that my brain needs retraining. It should be out in May and I'm hoping for good things.
I agree Jaycee...a good placebo is what I need!
Love your story Lauren!!
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Clearly there are multiple ways cancer can progress from Ibrance-Femara treatment; we know of ESR mutations in the estrogen receptor activate the pathway in the absence of estrogen, so that AIs may no longer help (but Faslodex can work), whereas PI3K mutations and FGFR gene amplifications cause up-regulation of CDK4.6 activity so inhibiting these pathways might restore the sensitivity of the cancer to anti-estrogens. Another way recently reported is mutation of HER2 (rather than gene amplification, which is what gives rise to HER2+ status), and they say that responds to Faslodex-Neratinib. http://www.onclive.com/web-exclusives/acquired-her...
Those genetic tests are important after progression, we need to know what happened..0 -
Thanks Cure-ious....I always store your info away for the future.
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