Ibrance (Palbociclib)
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And here is Constantine's iconoclastic view of how to work your way through the current endocrine and targetted therapies ... for SLOW moving cancer. He points out that these treatments take up to 6 months to work so it may not be the choice if your cancer is moving quickly. In an case, some strategies to think about from a smart person.
From Constantine/Edgerider
I would counsel on the best evidence, plus consensus with many of my oncology colleagues, that the best motivated sequence might be something like this, assuming we are at the point of deploying immunotherapy:
1. the CDK4/6 inhibitor palbociclib (Ibrance) + letrozole (Femara)
upon progression, then:
2. the CDK4/6 inhibitor palbociclib (Ibrance) + fulvestrant (Faslodex)
upon progression, then:
3. the CDK4/6 inhibitor palbociclib (Ibrance), but adding - an off-label indication - BOTH letrozole + fulvestrant
upon progression, then:
4. the mTOR inhibitor everolimus (Afinitor) + exemestane (Aromasin)
upon progression, assuming some appreciable level of response to any previous CDK4/6 inhibitor therapy, then:
5. the CDK4/6 inhibitor abemaciclib, either now on clinical trial, or after FDA approval, depending on timing.
This strategy - rather than early cutover to an experimental agent has a unique virtue: CUMULATIVE prolongation of life: assuming a conservative estimate of no less (some may be longer) than 6 months duration of response (DoR) for each of the first four options above - including in later-line settings, that would accumulate to no less than 2 years collective DoR, and add to that no less than approx. 9 months DoR for abemaciclib (8.6 months in the MONARCH 1 trial), and with almost one third (28.2%) of the trial population out to no less than 12 months (I drilled down the raw trial data), then we have "picked" up no less than about 3 years total cumulative duration of response (DoR) across this sequence, and bearing in mind that these are MEDIANS - meaning that fully HALF of the patients exceeded these numbers - then we could have outliers to the 5 or 6 year point or beyond (in that sense I have argued to treat all non-curative cancer as a CHRONIC disease, not as a "terminal" disease, as I know of dozens of metastatic patients now out to 18 - 25 years survival)).
No other bio-endocrine sequence (without chemotherapy) would result in such a high "therapeutic ROI" - Return on Investment, as it were. And in a previous posting I have already argued and documented the case for "waiting on stable" or "running on stable", and I proposed that we need to expand the conventional concept of OBJECTIVE RESPONDERS (CR or PR) to STABLE RESPONDERS, since I have put forward somewhat revolutionary evidence that stable disease is associated with comparable overall survival to those achieving a so-called objective tumor response (complete or partial).Constantine
Constantine Kaniklidis
Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)
Breast Cancer Reviewer, Current Oncology0 -
I'm starting Ibrance tomorrow, alongside Arimidex. I got the results of my CT scan today, nothing outside of my liver, the large spot has shrunk, two small spots have grown, and there's a new 7mm spot. So my Doc is adding Ibrance.
Going to start at the begining of this thread and catchup with you all.
Sarah
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thanks for sharing that z! It gives such hope reading this. I want to follow up that my Dr. Whom I see for the trial said that I should follow through with the biopsy fro my irregular pap. They did say I should try and have a one on one discussion with my obgyn first. They scheduled me for a biopsy on March 1st. I have a call into my dr. Waiting for a call back. I have my first scans on March 2nd. I really would just like to wait in the biopsy. I think this is what I am going to talk to my gyno about. What do you all suggest. I just hate to have another test so close to my scans. It is just more stores. These will be my 1st scans after starting tx for mets dx
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Apg - Better safe than sorry on the pap tests. However, I am still choosing the "head in the sand" option. I cannot deal with one more medical procedure. May your pap biopsy be clear, your scans awesome and your spring stress free. Much deserved.
>Z<
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I wanted to let this thread know that my wife passed yesterday due to cardiac arrest after a long. Battle with cancer for 6 years and MBC FOR 18 months.she deafeated cancer and did not let cancer win .I AM SHATTERED BEYOND LIMIT BUT WE WE HAVE WON AGAINST CANCE
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Many-
No words can take away your pain and sense of loss. I am sending you all the strength my body can give, warm hugs and calm silence that let you know we care. I haven't been a part of this forum for very long, but I can see it is a caring place with knowledge and support. I hope you know in your heart what you meant to her. I wish there was no loss and certainly no MBC. May god take you in his hands and protect and guide you to a place of peace to honor this wonderful woman. Sending prayers and strength always. ~
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many - I am so sorry about your wife. My heart goes out to you. Sending you hugs.
Cathy
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HEy there! I started Ibrance and leterozole a week ago. Just discovered that I am now METS. Ive always been able to kick it...or at least think that I had. I only have cotten mouth so far and feel kind of sleepy last two days but not sick. How are you?
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Many - I am so sorry for your loss. Your wife was courageous and a model for all of us. It is very kind of you to think of us and let know of her passing. Everyone here matters to all of us and every loss is painful.
>Z<
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Ajones - Welcome. I don't know what METS are but whatever it is we'll help you through it. Can you explain?
>Z<
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Many so sorry about your wife passing may God give you comfort and peace knowing she's in pain no more. (Hugs)
Aurora
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many, this must be a terribly difficult loss for you. My heart aches, and I know that your wife must have been an amazing gal.
Peace be with you, MJH
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Many, I am so very sorry for the loss of your wife. I hope you have a great deal of love and support around you. May G-d bless you.
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Many, may I add my condolences to everyone else's, I'm so very sorry for your loss and pray that God will comfort you and bring you peace. It is very kind of you to let us know about your wife. I'm glad you said she won against cancer. I also have a heart problem and pray that's what takes me and not the cancer. May God bless you and your family with peace
Faith (in the future)
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Many......so sorry for your loss. Lots of love and prayers to you.0
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Ajones,
I have been on Ibrance three full cycles and a week into my fourth. I take it three weeks on and one week break, on that week break I feel pretty good . I have bone mets in my right pelvic region only and have had a crazy ride with this since diagnosis. Went from stage II one week , to stage IV the next.
I was lucky to have some surgery to remove the majority of the cancer. But have had heavy chemo. Lots of it. The ibrance has been pretty easy considering it is chemo. I get some joint pain,some headaches, just over all tired and fatigue is my biggest problem. I also take anastrazole daily and sometimes you can't figure out what medicines give you what side effect. My medicine shelf looks like a pharmacy close out special. I have mild pain and take Percocet to help. I find the chemo causes some constipation, let's face it any medicine does at this point. I swear by Mirilax it works like a charm every day. Suffer if I don't. I also get a monthly shot of Xgeva. Learned to take Claritin two days before shot and two days after. TO prevent awful bone pain and side effects , which can be awful. Works for nulasta also. Hope everyone feels well as we can. Talk a nice walk, depending where you live of course. Happy weekend.
Many~you are in my prayers still.
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tHank you for writing back! I went into surgery thinking I had a second recurrence and woke up with the doc telling me they didnt remove the lymphnode because they found another place on my chest wall and I am now considered MEtastatic stage IV. I freaked out for two weeks and was up and down and I finally got myself together and really had to because I have a nine year old boy and needed to keep it together. after meeting with a few different hospital oncologists, Im now on Ibrance and Leterozole. Im still working and feel pretty good. So, do you get a scan every so often? Are you on a certain diet? I have been assigning people/friends to research foods etc. I am doing no sugar, no flour, no wheat and all organic and all fruits and veg but I am about 80 good and 20 bad foods at the moment. I just cant do 100 percent you know? I get a scan to look at the three areas in 5 weeks to see if they are gettting smaller or same or larger.
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Hello! I want to check in to see how you are?
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Ajones I don't have too much of an appetite. All food tastes like cardboard. I also try to stay away from sugar. But still love my sweets. I am also stage four but an odd stage four, I am just hoping that it stays stable which is what I was when I saw him last. I haven't had a scan since I've started ibrance. But since I'm going to have completed my fourth full course I am Assuming one will be ordered soon. My blood counts were what he was basing my stable commentary from. I sleep a lot. God bless you for being able to work that's wonderful. You are a fighter. my main problem has been fatigue. My kids are both older. One is 21 and one just turned 20. They are still like having a nine year old. Bless you and have a good evening ! Talk soon!
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Today after -3 days of her passing,I am not able to accept that she has passed ,I keep on searching her in my home/Garden/Washrroom ,I can't find her ,I can't leave with her,SHE WAS MY LOVE,MY LIFE ,I CANT LIVE WITHOUT HER
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Many
My heart aches for you. I wish there were words or a magic wand I had to make your pain ease. I know you can't see her. But she will be with you forever, in your dreams and memories. I hope my prayers and thoughts give you some strength to get through each day, until you are together again. I know the way the loss feels Isn't fair and I hate that this isn't fair at all. MBC is never fair. she is your own personal angel now many. I hope you have loved ones and family to hold and comfort you as I know we all we wish could. God bless you and your family Many......God bless.
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I just started Palbociclib with a drug called bazedoxifene. Its a study. I started Wednesday Feb 15, 2017. I have just developed a bad cold and was wondering if they would have me stop the drug for a bit. I have not called my study nurse yet.
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Many - my heart goes out to you. Please look into some grief counseling to help get through this - your wife would want you to be happy again. Micmel can you post your treatments and dates so we can weigh in? Ajones - you are still new to Ibrance +femara, so lets see how you do with your next scan. Hoping you are stable. After 15 rounds, I am still working full time, but uber to work on days I feel tired. That helps me a lot, plus I eat mostly organic, little meat, a glass of wine as needed and ice cream! Planning a Seine river cruise to Paris & Normandy in July - something to look forward to with my RN sister. Getting big travel in now.
(()) Claire
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Many I don't know if you are a believer in prayer or not but I'm going to include you in my prayers. I pray that you find peace and comfort knowing your wife is resting now. Like someone else suggested look into some grieving counseling as it is a process.
Aurora
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many, I am so sorry for the pain you are feeling right now and will keep you in my prayers. I pray you have others around you to support you through this. Claire is right that grief counseling could help you. While none of us know what you are going through, I pray you can find some comfort in all your wonderful memories and also by knowing that your wife is no longer in pain.
Hugs, Faith ( in the future)
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Many, I am so sorry for your deep and intense pain. I don't know if you are religious but I wonder if reaching out to your pastor may be helpful. I also encourage grief counseling, either individually or group. I know these suggestions will not take the pain away but they may provide some small comfort at such a difficult time.
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((Many)) - It takes strength and courage to feel as intensely as you do, to be present with your tremendous grief. Take care of yourself. At some point you will get through this, the pain will diminish and your wife will be with you in spirit.
>Z<
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For those following the development of the 3 CDK 4/6 kinase inhibitors, I am going to repost some comments from Elizabeth (EV11), one of my favorite posters on Inspire. She is a practitioner with cancer at a major research hospital and her doctors have been running various trials of CDK 4/6 inhibitors for years. She is well positioned to learn things and trained to understand them and highly motivated to stay on top of things by her own MBC. I am excited about abemaciclib, but it looks like it will be tough on the tummy. Progress on the horizon, but no magic bullet.
>Z<
CDK4 and CDK 6 (Cyclin Dependent Kinases) are enzymes that play a part in the cell reproduction/replication process. For breast cancer cells that are ER+, the action of estrogen binding to the estrogen receptor (ER) starts a multi-step cell reproduction process. The primary (and easiest) path for the cells to use go from ER through the CDK4 (and to a lesser extent CDK6 ) paths a few steps later. Cells that lack ER don't use CDK4/6 very much, so these are not a good medications for those cancer cells. They use different path for reproduction.
Abemaciclib appears to have more CDK 4 activity than do the other 2, and also less CDK 6, which is why it has less impact than the other 2 on blood chemistries (WBCs/RBCs and platelets are heavily engaged with the CDK 6 path in their cellular development). But abemaciclib trades less hematologic impact for much more (and in some cases very uncomfortable and unmanageable) GI side effects than the other 2 drugs cause. My onc, who is a PI for some abemaciclib trials, reports that as many as half of her patients have required dose reductions and a few have dropped out of the trials due to persistent, significant diarrhea and cramping, even with anti-diarrheal regimens....). She does say that it alone of the 3 "-ciclibs" appears to cross the blood brain barrier and may be useful in treating brain mets...nice...
She's not sure if there will be enough distinctions between the 3 drugs to perhaps use 2 or all 3 of them sequentially, or if they are similar enough in action that developing resistance to one will confer resistance to the others. She tends to think that ribo and palbo will be similar enough to be interchangeable and not of use when the other one fails, but there may be enough of a difference that abemaciclib might be a good next choice. In her mind, it would be used after either palbo or ribo, since they have less CDK 4 activity. However, she's not sure that there is enough difference in their action that insurance companies would approve one following the other when there is progression (although switching between them due to their different side effects would likely be approved in order to find the most tolerable drug). But there is already one ribo trial about to open (on the east coast somewhere, she says) that is accepting participants who have progressed on palbo, though, so there might be trials that we can get into in the next few years once we run through Ibrance.
Palbociclib and ribociclib need to be used in conjunction with ER blockade (both have significant CDK 6 action, and perhaps less CDK4 impact than abemaciclib, and they don't have much effect as mono therapy). Abemaciclib seems to be much better as a stand-alone drug, but shows good activity with ER blockade also. For all of these meds, using a medication that blocks the production of estrogen greatly limits the amount of estrogen available to bind to the ER, and blocking CDK4/6 prevents those cells that do have estrogen binding to ER from completing the reproduction cycle...thus disease is at least held stable, and if other process are able to work, the cancer cells can be killed by external mechanisms or die because internal activities are interrupted, and tumors can shrink or disappear.
Unfortunately, cancer cells are optimal examples of evolution, and over time there are cells that can learn to find a detour around ER and/or CDK4/6 paths to engage the reproduction pathways at later stages, and those cells become the dominant metastatic drivers--that's when we say that the cells have become resistant and we need to move on to another class of medication --Thus the role for the other meds currently available or in trials (i.e., those that act on mTOR, PI3K, HDAC, or perhaps immunotherapies, radiation, chemo...).Elizabeth
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Thank you for posting this Z. Very informative.
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I started my Ibrance today!! I was on this for 10 months last year and lost a lot of hair, so I am not excited about going through that again! But if it can keep my cancer in check.....then I will have to deal with thin damaged hair!! Who knows...maybe I will be lucky this time and not lose any!! I am getting the Ibrance from a different pharmacy this time and the pill looks different, so I am crossing my fingers!!
>Z< interesting read on the CDK4/6. Thanks for posting!
Robin
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