Ibrance (Palbociclib)
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I am desperate for suggestion on how to handle the incredibly painful foot issues I've developed. I don't think hand and foot syndrome - it's not the skin. I wasn't thinking neuropathy - it's not tingling numbness. It's downright horrid pain anytime I start to walk. I have to hobble around and the only relief I can get - and it's small but worth it - is putting on shoes that are well-cushioned. I'm blaming the letrozole for this, and maybe after effects of the Taxotare/Cytoxan regime I was on last year.
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So I had my scans on Friday and just got my CA 27/29 results. Everywhere is increased metabolic activity with the lung lesion increasing slightly. The neck node actually went down some in size. I have new pathological fractures in my right 4th, left 7th, 5th and 9th rib. I have so much pain here so that is understandable. New subtle lesions in my liver with increased activity. The PET scan reports worsening metabolic activity everywhere.
So what my MD wants to do is to knock it down with Taxol and Avastin. I did this combo in 2007 and was in remission with Aridimex for 6 years with CA 27/29 in the teens for 6 years. The 2nd choice is Abraxane and 3rd choice is Gemcitabine. My CA 27/29 score went from 233 last month to 219. What to do.....Use the TM and wait another 3 months on Ibrance/Letrozole or knock it down with all the increased metobolic activity and go straight to Taxol and Avastin. I am waiting to hear from the MD in Alabama on this thoughts.
I am scheduled to start radiation on my sternum, left ribs, humerus and tail bone tomorrow. I have had the worst pain in the last two weeks than I have had in all the 11 years I have dealt with cancer. Shoot - I have only been on this combo since November still at 125 mg., great labs and no real side effects that are a bother. Ideas? Thoughts?
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In this situation, I would go with my onc's advice, relying on his/her experience and intuition about how this cancer is behaving. If you don't trust them that much, then get a second opinion. If you decide to start chemo right away, could you pause on the radiation and see if the chemo works quickly to relieve the pain instead? I've already decided that if taxol is ever suggested again for me, I will say that I have paid my dues with all that benadryl knocking me out for the day and the steroids keeping me up all night, and that I want abraxane.
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Jen, that sounds awful. How about consulting a palliative care specialist?
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Shetland - I wish I wasn't questioning things, the lower CA score threw me. It will be interesting to see what the other MD has to say. They usually are on point together. If remember right I didn't have any issues with Taxol in 2007 but it's another 10 years except for hair loss and bone pain days in. I wouldn't want the Benadryl ride. How was Abraxane side effects?
Jen - it doesn't sound like Hand/Foot Syndrome. I had that for almost a year. Took 3 months to fully recover. How about Plantar Fascia? I had that once and it was very painful. Hope for the best.
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Lisa has a good point, Jen. Maybe the foot pain is not drug-related. Or even if it is, a podiatrist might help.
Lisa, I had Taxol. As you may know, patients receiving Taxol are given Benadryl and steroids to stave off allergic reactions to the solution the paclitaxel is in. Abraxane contains the same drug, paclitaxel, but in a different carrier, so the anti-allergy drugs do not have to be given routinely. It is more expensive, so they usually reserve it for people who cannot tolerate Taxol. If there is a difference in efficacy, it is small. Ask your onc for the latest on that.
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jensgotthis: I had the exact foot pain you describe when on Femara in 2012-13. My oncologist did not think it was caused by the AI and thoughtt it was probably Plantar F. I love and trust him but I felt sure it was. Because of extreme foot, leg and hand pain I stopped the drug and had complete relief within a few months. I made the decision to stay off Femara knowing that the cancer could recur. (Sometimes we must do things strictly based on quality of life!) The BC recurred in September, 2016, and I still have no regrets. The good news is that I'm on IBrance with Arimidex and, so far, do not have the AI pain issues. All that to say, perhaps you could switch AIs? Good luck, my friend.
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jengothis: I am a twin to PatgmC on this! I developed plantar fasciitis in both feet, which apparently is unusual for it to come on at the same time for normal plantar fasciitis, after seven years of AIs (Arimidex and Femara)- I was doing the stretches they recommend for it and got custom soles but nothing worked, I hobbled all around europe on a long trip and had it for a total of about 16 months when I became convinced that it was the AI. Hard to explain why, but it seemed more than plantar, I had the strong sense of feeling poisoned, was developing carpal tunnel as well, which could have been unrelated. Anyway, I went off and boom it slowly but surely corrected and was all gone within a month or two. Never came back, although the cancer did. I am convinced it is an SE that can show up after long-term AI usage. Though of course it could be normal PF..
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Has anyone had a rash with Ibrance.l? I am on day 13 and have a palm sized rash just under my bra strap. Any tips on getting rid of it? Used cortisone without success.
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Cure-ious (aka my twin!): That's exactly what I said, "I feel like I'm being poisoned!" I have a walker in my garage that I knew would be needed soon as I had started to fall and I made the decision to retire from a job I dearly loved. What a relief to find the side effects stopped so soon! I've had many friends who struggled with one AI and switched to another which caused fewer problems. I pray that Arimidex continues to be kind to me. So far, so good!
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Bekadawn: I had a mild rash from my ankles to mid-calf for the first 3 months. It wasn't terrible, just odd. I never treated it and now it's gone.
I decided it was just to let me know I was really getting the drug and not a placebo!
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Jen- I get incredible pain in my feet and calfs. Common side effect of letrozol. I take 2000 mg. of longvida circumin daily. Cannot walk when I stop taking it. Going for a run now. Doesn't work completely but enough to allow regular intense exercise.
Must be a liposomally encapsulated form or some other trick to make it bioavailable. Otherwise you just get spicy pee.
Z
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Mediclisa - That scan report is particularly devastating given that it was so unexpected but the good news is that chemo is incredibly effective when cancer is on the move. But take Shetland's advice and insist on Abraxane. You are in my prayers. Whatever chemo you choose will make short work of this new growth.
Bekadawn - I had rashes and psoriasis and all kinds of weirdness in the beginning adjusting to the protocol. Whatever your favorite detox strategy will help if you do it regularly. Sauna, dry brushing, exercise. You have to do something on a daily basis to move the drug metabolites out of your system.
>Z<
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Catching up on some old posts in this FAST moving thread.
Shetland - Thank you for clarifying the relationship between PR- and tamoxifen resistance and endocrine resistance generally. That instantly organized a whole set of confusing research papers I read in my head.
One of my oncs that is generally on top of things says that the endocrine receptor needs a functioning progesterone receptor to work. Since I have no progesterone receptors, he believes hormone suppression is doing nothing for me. He thinks that Ibrance and the complementary therapies are what is controlling my cancer. It's a relief to find that isn't entirely supported in the literature, especially after your clarification.
I am meeting with that particular onc next so it's good to have that counter-argument sorted out. I am sure it comes as no surprise to you that my oncs take a lot of heat ... but they seem to look forward to talking with me.
Micmel - We need you on the Stage V Fitness thread. Hope to see you there soon.
>Z<
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thanks zarovka and good luck to you Lynne. My sister didn't get a port, and wished she had. When first diagnosed with met my first question was could I get one
My onc is very up. He talks like this is a total cure....Just hoping it will work for that 22 month! Thanks again for all the support. Day 8...Need to get the bucket list written, then done.
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i mix up vasoline, jojoba oil and shea butter and slather it anywhere I am dry or flaky.. bees wax and coconut oil helps too. There are meds out there but if the stuff works on baby's butts .... I'm on day 8 and very dry skin along and dehydration headache are my first symptoms. The sauve I carry around with me. Headaches go away once I drink water, but hit me when I get up in am
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Pinkpunk - Ibrance will not be the total cure for most people. But it buys time to get to a cure and it is relatively easy. Hope it buys us both a lot of time.
>Z<
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Lisa
I had 9 sessions of abraxane because I am allergic to steroids and onc chose the sister of taxol. It wasn't pleasant , hot flashes, terrible immediate hair loss , I had weekly sessions for 3 weeks then 1 week off for a break, it was rough , just when you feel half decent it was time to have more. I handled the chemo well ,noticed such exhaustion and fatigue and just never feeling well. Weakness in my legs and slept constantly . The worst thing for me turned out to be the neuropathy in my feet first, then in my finger tips. Quite challenging and painful. Never nauseous, some headaches. I had three sessions and had an allergic reaction and my throat started to close up, I have never seen nurses move so fast. They were wonderful. They were forced to add Benadryl pre Meds from then on out. It was tough but you can do it. I was glad when i was finished with it. I hope you do great on it. It is less aggressive then ac.
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Thank you all for your thoughts and prayers! I'll send an update. I am having my echo, tomorrow, to see if my heart can handle Doxil. If all comes out well, then I'm sure they will be scheduling the port soon. Originally, they scheduled the surgery for yesterday, but I didn't even have my echo yet. Why have it put in, if I wasn't able to do the treatment. 12 years without one (4 1/2 stage 4)! I had my "chemo talk" (3rd one!) with the nurse yesterday. Now just waiting on everything.
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Lynne, I am sorry to read about your progression. I hope that your echo results are good, the port surgery goes smoothly, the SEs from your new treatment are minimal, and Doxil kicks your cancer to the curb. I am looking forward to seeing updates from you.
Hugs from, "the other NH Lynne"
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Thanks, Lynne!!
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Hey Z, Your one ONC there is wrong- estrogen and progesterone are separate signaling pathways, each of course has its own receptor that it binds to in the cytoplasm, moves to the nucleus to turn on (or sometimes turn off) specific genes. The ER or PR binds to specific DNA sites in the gene promoters. Some genes are co-regulated by ER and PR, but that is a minority. More commonly, ER signaling causes an increase in PR, because ER can turn on the PR gene (other things can, as well, but in many cell types PR expression is a readout of ER activity). Therefore, if ER levels are high but PR levels are low, it can mean that the ER is not very active, ie not turning on a high level of PR. However, there are lots of genes ER turns on, and PR is not the strongest one, so it doesn't mean ER activity is dead. The state of the cell is as if the ER activity is relatively low-ish, and so you respond to AIs, but not as strongly. Luminal B cancers with PR- are more sensitive to Ibrance, so most likely it is working great for you (and me, I hope) but I wouldn't drop the Femara!! Cheers, K
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Cure-ious -
Thank you so much. I am going to sound like I understand cell signaling. Let's pray he doesn't ask any questions.
I remember well that you mentioned that Ibrance should work BETTER on my Luminal B PR- cancer and I hang on to that like a talisman agains progression. Gave me a lot of hope, but I like data too. Now I understand why, mostly. You obviously have some background in biology that I do not.
Something is working. Got my Biocept results today and my CTC counts are zero. Not exactly sure what that means. It's a weird and poorly understood test. But it gives me more confidence buying plane tickets for the summer vacation.
>Z<
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Whoo-Hoo! What's a biocept test?
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Biocept is one of several companies that analyzes circulating tumor cells (CTC's) in blood. Interesting idea but we don't really know what they mean clinically. I am going have it done periodically. Experiment a bit. Would have been a more interesting experiment if they found cancer cells, but probably(?) better for my life expectancy that they did not.
>Z<
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Z, what is on the Biocept report? Does it list specific genetic mutations?
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Z - I love that you are ahead of the curve and planning a summer vacay! Does the biocept report measure cancer cells only in blood or can it measure lymphatic activity? What is used for the test - blood vials? Very curious here and want to know more. FYI when the fluid in my lung was first analyzed (the pleural effusion signaling I was Stage 4), the % of ER/PR cells was analyzed in the report. I found the info very helpful and noted that I did not have a large amount of cancer cells present, but enough for my TM to register 40. Sounds excellent if you are at 0, but possibly there are lymphatic markers not measured by this test. Either way yippee for you!
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Lynne- Good to have a plan in place to address progression. Still crummy to have it happen!
Z- Great news on the Biocept test! Sounds interesting. Buying a ticket is the best medicine
. Looking forward to something keeps megoing.0 -
Biocept is a blood test. Foundation One also has a blood test that looks at circulating cells. There are 8 companies developing liquid biopsy tests I think they all can look at acetite fluid as well, but not my situation so I don't know.
No one seem to look at lymph. That would be a good place to look. Are there tests for that? Maybe it's hard to get a sample if you don't have ascetites. Zero circulating tumor cells certainly does not mean there is no cancer moving around, but it seems to be associated with better prognosis.
My doctor ordered a specific test for the BRAC mutation and that came back negative. I don't know where they got the sample if they found no tumor cells. Maybe they look at free floating DNA in the blood for some of their genetic tests? Like I said, I agreed to this test to learn. I am still on the steep part of the curve.
He also ordered a breast panel which was not done. I am guessing that requires tumor cells to execute. I know that looks at the current hormone receptor status and it might have looked at more mutations.
The cost for what I had done (minimal genetic testing) was $250 and covered by my insurance. It may turn out to be less since there were no cells to do pathology on.
>Z<
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I am repeating this summary of the evolving state of ERPR+ treatment options from Constantine aka Edgerider on Inspire. Found it helpful. Abemaciclib seems very effective on heavily treated cancer. Those of you have moved on to chemos will have a potentially easy treatment to consider.
From Edgerider/Constantine, not me.
I will here take up two most promising CDK inhibitors, ribociclib, and abemaciclib, the latter of which I favor heavily, for reasons I will develop below in assessing it as frontier-edge in efficacy and promise. I will also respond to several contributors like my dear friend BentonCity and several others, but I will first discharged this, an IOU from my previous posting, emphasizing points not mined in the general medical reporting that misses so much:
RIBOCICLIB
The Phase III MONALEESA-2 trial evaluated the use of the CDK4/6 inhibitor ribociclib (formerly, LEE001), with or without the AI inhibitor letrozole (Femara) in patients with metastatic ER-positive disease. Noting, importantly, that this was only in the FIRST LINE (NO previous treatment for advanced/metastatic disease), the interim analyses data on a median follow-up of 15.3 months with after 18 months, 63 percent of women treated with the combination having disease that did not get progress, representing a 44% reduction in progression-free survival events, and with activity emerging early on in the treatment cycle, and with primarily hematologic toxicity that was largely asymptomatic in patients. Based on these promising findings, ribociclib in combination with letrozole was granted an FDA Breakthrough Therapy designation (which generally entails the drug's more rapid time-to-market after FDA review and approval).
In addition I should note that preliminary data reported at SABCS 2016 from a two-arm trial of ribociclib combined with both the mTOR inhibitor everolimus (Afinitor) and exemestane (Aromasin) in postmenopausal women with metastatic disease that is AI/endocrine resistant, has found 1.8% CR, 9.1% (3.6% confirmed) PR, and a disease control rate (non-progressive disease of 70.9%.
And another triplet trial (reported at SABCS 2016 and ASCO 20127) in first-line, treatment-naïve patients, ribociclib plus the PIk3 inhibitor alpelisib in combination with letrozole (Femara) resulted in an objective response rate of 39% and a clinical benefit rate (CBR) of non-progressive disease of 73%, but I note that in patients who had received any previous treatment, the objective response rate was only 5%, with a clinical benefit rate (CBR) of 32%.
CLINICAL LESSONS LEARNED: RIBOCICLIB
For me, unless other clinical data emerges, then the evidence to date supports that:
1. Ribociclib is best deployed and RESERVED FOR the FIRST line setting ONLY, in contrast to palbociclib (Ibrance) - (and abemaciclib, below) - that has already in the PALOMA trials, exhibited strong and undisputed activity in LATER-LINE settings (even in third line and later) when deployed as Ibrance + fulvestrant (Faslodex), which, note, is authorized and approved for use ONLY in SECOND and LATER-line settings, after progression on previous endocrine therapy.
2. at present, coupling ribociclib with an AI agent appears to most prudent strategy.
ABEMACICLIB
Preliminary data from a phase I study of abemaciclib [SABCS 2014] in patients with five different tumor types including HR-positive metastatic breast cancer, with I note a median of seven prior systemic therapies (outliers out to 11 lines) found an objective response rate of 19% and a disease control rate (including stable disease (SD) under RECIST definition of >24 weeks of ) of 81% for HR-positive MBC patients.
This Phase I study was expanded to evaluate abemaciclib plus fulvestrant in HR-positive MBC [ASCO 2014.] with patients having a median of four prior systemic therapies (and outliers out to the eight line), finding an objective response rate of 62% confirmed PRs.
A subsequent Phase I study [Tolaney et al, J Clin Oncol 2015;33(Suppl 1).] of abemaciclib in combination with different endocrine therapies for HR-positive MBC (median lines of treatment = 3, with outliers out to 8) demonstrated a disease control rate (CR + PR + SD) was 67% for those on abemaciclib + AI therapy, and 75% for those on abemaciclib + tamoxifen.
The phase II MONARCH-1 trial evaluated abemaciclib MONOTHERAPY in HR-positive, HER2-negative MBC patients with a median of 3 lines of prior therapy for advanced disease, including a median of 2 lines of chemotherapy (as opposed to endocrine or biological therapy) for advanced disease, yielding an objective response rate (ORR) of 17.4% and a clinical benefit rate (CBR) of 42.4%. What's important to remember about MONARCH-1 is that many women in the study had already received multiple lines of endocrine treatment (median 3 - 5 previous lines in the metastatic setting, with outliers beyond that), developed resistance and were refractory to all of these treatments, AND progressed, many of whom also received chemotherapy, and these results were for MONOTHERAPY in a heavily pretreated population, which as I determined through examination of historical controls with any other agent achieves at best only 10 to 20% clinical benefit rates - half of that achieved by single-agent abemaciclib, and with responses of short duration.
Hence, the collective results of these trial, including MONARCH 1 (MONARCH-2 (with letrozole) and MONARCH-3 (with fulvestrant) are in progress, and I expected some preliminary results by summer) are exceptionally exciting., and accordingly it received a Breakthrough Therapy designation from the FDA in October 2016.
WINNER: BREAKTHROUGH SURVIVAL
In addition, for me, the overall survival (OS) of these heavily pretreated MBC patients was 17 months, and that compares to historical control I review from ALL clinical trials to date, as significantly better than other survival results, which are usually are at best 13 months. Thus, consider that for the current champ, eribulin chemotherapy in this setting, the EMBRACE trial achieved a median overall survival (OS) was 13 months, we clearly have here a major advance and improvement in overall survival in the highly challenging later-line settings (past at least 3 lines of therapy).
HIGH TOLERABILITY
The major limiting constraint with all CDK4/6 inhibitors to date, like palbociclib (Ibrance), is their most common adverse effect, that of myelotoxicity via neutropenia (low WBC neutrophils), with palbociclib (Ibrance inducing some degree of neutropenia in over half of women on it, with associated dose interruptions and sometimes dose reductions, a toxicity that so fat from the available data seems to also afflict ribociclib.
But abemaciclib evades a good deal of this because although strictly a CDK4/6 inhibitor, it is more specific in inhibiting CDK4, that is it is CDK4-selective, and myelotoxicity including neutropenia is primarily associated with CDK6, making the incidence of neutropenia on abemaciclib significantly lower and more manageable.
CLINICAL LESSONS ON ABEMACICLIB
And unlike palbociclib,
1. abemaciclib has strong single-agent activity in HR–positive MBC,
2. has durable response in later line settings,
3. a good tolerability profile with reduced neutropenia, and
4. to date the highest OS in these challenging heavily pretreated settings of any oncotherapeutic agent, whether endocrine therapy, chemotherapy, or biological therapy.
ACCESS
There are currently 14 NCI-registered trials,
https://clinicaltrials.gov/ct2/results?term=abemaciclib+%22breast+cancer%22 &Search=Search
ten of which are actively recruiting now, either as monotherapy or which various combination of agents - Letrozole, Anastrozole, Exemestane, Tamoxifen, Everolimus, Trastuzumab; Fulvestrant , or with LY3023414, which is a dual PI3K/mTOR inhibitor, but note that it is also available through Lilly's attractive Expanded Access Program (EAP):
https://clinicaltrials.gov/ct2/show/NCT02792725?term=abemaciclib&rank=24
active and recruiting currently in three US locations (California, Missouri, and West Virginia)
A FUTURE OF PROMISE
Besides these, we also have the oncological mTOR inhibitor everolimus (Afinitor) in various combinations with endocrine agents (including the FDA-approved exemestane combination), and with fulvestrant and others in clinical trial, and the non-oncological mTOR equivalents like statins, metformin and pharmaceutical-grade monacolins/lovastatin-standardized RYR (Red Yeast Rice).
In addition, outside of both the CDK inhbitor and mTOR inhibitor class, we have some very promising immunotherapeutics, like the PI3K inhibitors, like:
PI3K INHIBITORS
- Buparlisib (BKM120), an oral pan-PI3K inhibitor
- oral alpelisib (BYL719)
- oral pictilisib (GDC-0941)
- oral taselisib (GDC-0032) - especially as being tested in the LORELEI and SANDPIPER clinical trials, and whose performance for me makes it the most promising of PI3K inhibitors on the frontier edge
which I reviewed and evaluated in an earlier part of this very thread on Inspire.
We also have new directions in HDAC inhibitors, especially the broad-spectrum endostatin operating across multiple molecular pathways, which has also recently received FDA Breakthrough Therapy designation for breast cancer. And dozens of other pathways like PD-1/PD-L1 (Programmed Death) Inhibitors, CTLA-4 Inhibitors, LAG-3 Target Therapy, several antibody-based pathways (like OX40 and 4-1BB Agonists), as well as vaccine therapies, especially for - but not exclusively - HER2 disease, among many other biological therapies promising highly attractive alternatives to conventional chemotherapies.
OUTLAWS
So, we can all be Outlaws:
"Hope smiles from the threshold of the year to come, whispering, 'It will be happier.'"
(from Tennyson's The Outlawry)
Kind regards
Constantine
Constantine Kaniklidis
Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)
Breast Cancer Reviewer, Current Oncology0
