Abemaciclib Verzenio for Stage IV
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Some progress is being made on identifying biomarkers for response to CDK4/6 inhibitors (and luce-there is no way only 14% of luminal A cancers respond to drugs like Ibrance, don't know the number but it would have to be waaaay higher to get a doubling of response in the trials)
Here is a recent paper showing that certain mutations in Cyclin D1 gene, in breast and other cancers, can cause it to get amplified and those cancers respond particularly well to Abemaciclib.
https://www.ncbi.nlm.nih.gov/pubmed/29232554
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Zarovka: Thanks for your informative reply regarding monitoring! Yes, I agree on the immune system stimulation and involvement, and that it is the key. That's why it greatly concerns me what abemaciclib is doing to the gut microbiome, where the immune system presumably resides. One of my doctors (an MD, not an ND) believes that generally, the gut microbiome is the key to being, becoming, and staying healthy and alive. He recommends a high-dose bifidobacteria supplement. (Not that that is a cure at this time, of course.) Abemeciclib riding roughshod over the GI tract might ultimately not keep us alive longer, nor offer any chance of an actual cure, I worry.
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Luce - It is interesting that you mention Abemaciclib's effect on the gut. My primary treatment is immunotherapy at the moment so anything I do needs to complement the immunotherapy (enhance not depress the immune system). I've seen strong arguments in favor of Abemaciclib because of the PDL-1 inhibition ... takes the breaks off the immune system. I considered doing it as a single agent through the treatment. However, the gut issue is a concern. For the moment I am watching and waiting.
Probiotics are one way to go. The problem is that the bacteria are never really going to set up shop and thrive in your got with the constant armageddon going on. Same problem with chemo. I take a Japanese product called Chitsu which is basically lactus bacteria broken down by enzymes found in soy. Basically the product is broken down bits of bacteria. It gives you some of the effect of these good bacteria even if your gut cannot support the ecosystem.
Viome is an interesting test. The provide the most comprehensive profile of the gut that I have seen. Something to consider if you want to know if your gut is getting in the way of your health. You may find you have a healthy biome in there despite the diarrhea. That may give you some piece of mind.
I have had mild to extreme diarrhea for 3 months, ever since September and I haven't been on an standard of care. I haven't had time to figure out what is going on. Will be doing a Viome test soon.
It would be interesting to study what Abemaciclib is doing to the gut lining and how that might effect absorption and the immune system. So many things I would like to study ...
The truth is that we often don't see improvements in overall survival from treatments that are pretty good at getting rid of lesions. Like you, I suspect that the side effects are one reason for that.
>Z<
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Thanks so much for creating this post! I'm new to Abemaciclib (started a few days ago) after progressing on Faslodex/Zometa. I was bone-only for a decade until a recent scan showed a few small spots in my liver...hence, the med switch. I consulted with an IR at City of Hope yesterday who has requested an additional MRI to assess the full extent of the mets. That said, he recommended giving the Verzenio 6-8 weeks to determine efficacy before exploring localized treatment (I'm hoping for RFA). Upon the first dose of Abemaciclib, I had extreme nausea/headache/dizziness that was akin to motion sickness. I was fully expecting diarrhea based on the data from the Monarch-2 trial and I have an rx for Lomitil on hand. Didn't need it initially but I was sidelined by the nausea so took a couple days break and now I'm reattempting today with Zofran. My gut (pun intended) is telling me that this med may not be optimal as I too am underweight and not thrilled about compromising the microbiome. I'll be following this thread faithfully and will keep you posted on my SEs.
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Luce- The most recent studies show that Abemaciclib works synergistically with immunotherapy, and that immunotherapy in turn is very dependent on good gut bacteria and strongly stimulated by probiotics that have bifidobacterium, so your ONC sounds right. Apparently, we will hear updates from the first year of Abemaciclb-Keytruda next month, but for anyone taking immunotherapy its probably a good idea to add probiotics as well .
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This is the probiotic my doctor recommends and I use: http://www.customprobiotics.com/five-strain-bifido...
I've looked but not found anything comparable anywhere. (I had been hoping to order at cost through my ND friend from one of her suppliers, but haven't found a brand that combines that many strains of bifidobacteria, or anywhere near that potency.)
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interesting, Luce! Are you taking Abemaciclib now? Because the probiotic/Bifido in preclinical studies had the same effect as a low dose of immunotherapy- and if Keytruda were also added, that combo might be very effective. Is your doctor part of a clinical trials hospital?
One question is whether we will even be allowed to take Abemaciclib after failure on the Ibrance-Femara combo, I'm certainly hoping so
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Z- What is up with you?! Still in Siena? When do you go back to Japan, world traveler?!!
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Also, Luce, did you notice any increase in neutrophil levels when taking the probiotic?
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Here is one of the 2015 papers that identified bifido as tumor fighting- note however it is for melanomas, which respond well to immunotherapy whereas MBC does not.
https://www.ncbi.nlm.nih.gov/pubmed/26541606
This shows bifido bacteria stimulate immune system function, including tumor killing activity, and helps patients get more benefit out of immunotherapy. Might do the same thing in combination with Ibrance/Abemaciclib, and all three could be better?
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Cure-ious: No, I am not on abemaciclib yet although I got my first prescription filled. I am still hesitant to take it. I am the type of person who before cancer (I had primary bc four years ago; the recurrence, a year ago) didn't even take an aspirin; I believe in holistic health, so messing with my gut and while blood count, etc., seems very counterintuitive. On the other hand, I'm dying of cancer (have been given less than six months, perhaps much less--I didn't ask for details), so something went very wrong with my body despite decades of presumably-healthy (who knows what actually IS healthy. In the 90s, it was soy) living.
I haven't had any bloodwork since starting those particular probiotics in November. Before then, I had been taking Garden of Life probiotics on-and-off for years, so not sure hoe much of a difference the new ones might make.
Not part of any medical trial; I refused standard-of-care treatment (tried Tamoxifen when I first was diagnosed but couldn't tolerate it, so zero interest in endocrine therapy. iI is unfortunate that my estrogen fuels my cancer, but the rest of my body needs my estrogen to be comfortable. No estrogen, no quality of life), so there are very few trials I qualify for. In fact, I haven't found one yet. I'm interested in immunotherapy, vaccines, oncolytic viruses...possibly metronomic chemo. But, again, for almost all trials, one has to be pretreated with standard-of-care chemo and such.
While some new meds should be available to us outside of trials on a compassionate-use basis, none of my doctors is willing to try to access them that way.
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Luce - That is a really interesting product but expensive. It's more than 4 times as expensive as the already expensive product I am using and probably 10's of times more expensive that making yogurt from a starter with bifido bacteria.
One question is whether all 5 strains are needed. In the study that Cure-ious mentions, the strains of Bifido that were found to be associated with tumor regression were B. breve, B. longum, and B. adolescentis and these 3 strains accounted for 99% of the bacteria.
I take Super Bifido Plus more or less daily. It includes three strains of Bifido (bifidum, breve and longum) plus the key lactobacilus and costs $35 per 30 capsules (100billion cells). I also make yogurt from live bacteria culture, various strains. The one that I linked to has all five bifido bacteria. Fresh yogurt is by far the cheapest way to flood your gut with good bacteria.
I am not sure why I take the probiotic, actually, after reviewing the impact of the fresh yogurt I make. I've seen estimates that you get 400M to 1B per gram of yogurt. I don't think I am getting 300Billion cells per day this way but I don't think more is necessary. I monitor my gut biome with regular testing. On this regime I generally find that 2-3% of my gut biome is Bifido bacterium.
Budgeting for what is important is key since a lot of the important treatments are out of pocket.
>Z<
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Cure-ious - Thanks for asking about me. I am in between trips to Japan ... going back in February. I am on ovarian suppression which is keeping my estrogen below detection levels. I am also going to Mayo to work with a researcher on SBRT to my sternum and liver with the hopes scaring a few tumors into releasing neo-antigens prior to my return to Japan. I will get a zometa shot next week, ostensibly to address the bone mets, but really because of its immune-modulating effect. I considered beginning abemaciclib prior to the immunotherapy treatment. I am concerned about the gut issues; however, it's on the short list for a maintenance standard of care therapy after Japan.
Otherwise I am sticking to non-standard of care strategies to enhance the immune system and control the cancer between treatments. I am concerned that the remaining standard of care options are immune suppressing. It's an interesting test of whether the strategies work. I will scan before I leave for Japan and we'll see how I did controlling cancer without following the standard of care.
Luce - I think very much like you do but, as you say, we have a serious disease and it isn't going to be controlled by sitting under a pyramid and drinking green tea. I have a strong complementary regime but I have been integrating certain standard of care strategies that I believe provide an overall advantage. The CDK 4/6 inhibitors are among the best in terms of efficacy vs damage. It is not the moment for me to take abemaciclib but I expect to start it in a few months and see if I can manage the gut issues. Odds are they can be managed with time through diet and supplements and perhaps some time under the pyramid. Seriously, managing stress is a big factor because stress alone can cause many of these symptoms.
In my opinion, based on the results we are seeing from trials, abemaciclib is the best FDA approved treatment for MBC available. I would go ahead and take it and see how you do. We are each very different in how we respond, one person will be able to make it work while another won't. I believe you will figure it out simply because of the way you think. You need to give it several months, 5-9 months. My experience with Ibrance was that the side effects were bad in the beginning but my body and the drug achieved a truce after a while.
What dose are you on? Be aware that is something that can generally be adjusted if you are having troubles.
>Z<
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Luce, thanks for the info about the probiotic. Expensive! But it looks good. I went heavy on probiotics on Xeloda (for 14 months) and avoided the nasty GI issues that most people get. It seemed to make a huge difference - when I stopped for 4 days, the GI issues flared up with a vengeance. Would recommend daily yogurt in addition to probiotic supplements. The yogurt seemed more impactful than the expensive, high-dose probiotics I used (I would rotate brands for more diverse pro-biotic exposure).
Curious and Z, very interesting about the immunogenic effect of probiotics. I have heard a bit about that and am convinced probiotics play a large part in many aspects of health, although it seems that it is not yet understood exactly the optimal balance in the "orchestra" of GI flora, as it is such an intricate, delicate balance. I wish there were just a simple recipe for that! There has to be a friendly bacteria out there that kills cancer cells or prevents their proliferation. I suspect the ultimate "cure" for cancer will be something much more simple than all of the intricate meds which are the focus now.
Z, for your return trip to Japan, will you be doing a full blown course of NKC therapy as you did before or some sort of maintenance or add-on therapy? Do you have any indications whether the first round "worked" or does that still remain to be played out?
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This is an interesting trial to consider with many locations.
This study is designed to evaluate the efficacy, safety, and pharmacokinetics of several immunotherapy-based combination treatments in participants with metastatic HR-positive, HER2-negative breast cancer who have progressed during or following first-line metastatic treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor such as palbociclib, ribociclib, or abemaciclib. The study will be performed in two stages. During Stage 1, participants will be randomized to fulvestrant (control) or an atezolizumab-containing doublet or triplet combination. Those who experience disease progression, loss of clinical benefit, or unacceptable toxicity may be eligible to receive a new triplet combination treatment in Stage 2 until loss of clinical benefit or unacceptable toxicity. New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.
JFL - Certain strains of bacteria turn on the immune system ... drugs fail without them and work with them. The presence of these bacteria has been shown to be as effective as a line of treatment on their own (follow Curious's link). The critters are generally but not always in the Bifido family. The data regarding the gut and immune response is already consistent and actionable. Any cancer treatment strategy that engages the immune system needs to start by focusing on their overall health which includes the gut. Why isn't this integrated into the clinic? No big pharma behind these amazing critters because there is no way to protect and monetize the idea that you need to make your own yogurt during immunotherapy.
The question of overall gut health is more complex but very important and also has answers. The overall gut biome can be evaluated and modified with diet and supplements. IMO, Viome does the most comprehensive analysis of the biome and provides a clear actionable report. I like Viome both because of the quality of the test and reporting and because because their strategy for manipulating the biome focuses on food rather than supplements. However, doctors have been using these studies for years. There are many solid tests and solid doctors using them. It is complex and probably not something one can figure out on one's own. I am pretty pro-active but depend on my practitioners for guidance on gut health.
Thanks for asking about me. I had a strong partial response to the first round of NKC therapy. I had a response that one would be happy to see from a round of chemotherapy, but the treatment was not considered successful because NKC count did not reach therapeutic levels. This means the response is unlikely to be enduring.
The low NKC may have been because I had an undiagnosed UTI during treatment. UTI's draw NKCs to the bladder where they get beaten up and killed by huge nasty urinary tract bacteria (or so I imagine it). Seriously, there is a paper on this. UTI's are nasty for the immune system and every cancer patient needs to watch for them. In any case, I had a decent response given that the immune response did not reach a level the doctor considers therapeutic. I feel its worth going back and trying again for a therapeutic dose.
I'll be better prepared, also. The doctor is focused on the NKC therapy and doesn't provide an integrated treatment plan designed to promote a response. This is not a cancer spa, it's a researcher with one particular tool that he is trying to perfect through working with patients in a clinic. The integration of the treatment into a larger plan is left to the patient. I didn't understand the treatment or how to potentiate the response as well as I do now. There is a huge cultural and communication barrier arranging the treatment. I knew coming in I wasn't getting all the info I needed for a successful treatment and I knew the only way to get it was to just go. You can consider the next trip a return, a re-do an add-on or just the second phase of a treatment that will, in my opinion, take 3 courses to complete.
>Z<
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zarovka: thanks for all the good info. i used to make kefir and yogurt and all kinds of other ferments for ten years but recently stopped because I'm too tired and also not very interested in food (and note: my daily homemade kefir did not prevent my recurrence), so taking probiotic supplements (and/or store-bought yogurt) is easier. I'll see if I can order the probiotics you take at cost through my ND friend; that would really help. I opted for those very expensive ones at this time since I am trying to enhance an immunotherapy treatment I had in Mexico in November and that cost me $40,000. Yes, I wiped out myself and my mom financially. That feels really shitty as that money could have bought her more ease in her retirement, and it looks like I'm still dying. The doctor had warned me that there was a 50% chance I wouldn't respond at all, so I'm not feeling cheated or anything, just sad.
I agree about stress relief but our lives can become extra stressful on top of even the cancer: For example, my boyfriend left me for someone else just before Christmas because he couldn't handle seeing me getting worse, although at the time there was a real chance of me getting better due to the treatment. Since then, it seems like my body has given up.
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Luce - Yogurt didn't stop progression last fall either but what you are looking for is the right combination of things. It's all a game of odds, as you know very well, and homemade yogurt is one of the cheaper ways to improve the odds.
That said, you've got the best standard of care drug that I am aware of sitting on your shelf. There is reason to be hopeful.
>Z<
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I made yogurts decades ago, but it seems now is the time to get back to it!
Luce's probiotic is expensive, but good, however I wouldn't want to take it continuously for a year or so, given that it could be blocking out growth of other good bacteria- too much of a good thing can be a bad thing? But I would take it if I really wanted a strong potential immunological boost when combined with some limited-time treatment that includes immunotherapy
Like Z, I'm pinning a lot of hopes on Abemciclib and for some good numbers to come out by combining it with Keytruda. Among checkpont inhibitors I like Atezo better than Keytruda, so perhaps that combo would work even better. And then just throw in some Faslodex!
So many different irons have been in the fire with regard to clinical trials we should be hearing definitive results (pro and con) soon-with luck we'll be able to look back and see that 2018 was a tipping point for us...
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Z- I'm guessing that your daughter cannot come with you to Japan?! And I bet she's really bummed about that!
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Oh hell yeah my daughter is coming. I am not going by myself and at 11 she is the only one with a schedule that allows it. She's get trained tomorrow on how to access my port. It's been quite a journey for the little munchkin.
>Z<
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Does anyone have a good guess as when to take my twice-daily probiotic now that I'm taking abemaciclib? The bedtime probiotics dose is easy: just before I go to bed, probably an hour or two after my last dose of abemeciclib and other meds. But I used to take the morning dose a half hour before food or other meds, just after getting up. Now I'm wondering if like with antibiotics, the probiotics ought to be taken, say, an hour or two after abemaciclib, once it's moved through my GI tract and been absorbed. Thanks!
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Fabulous, Z!! She sounds exactly like my daughter!! Totally in control of her life and mine!! When she was 13 she went with me on a meeting to Xiamen China (3-day science meeting) because they then treated us to a 5 day trip to xi'an and an area near Tibet, flew back home for two days to pick up my son who was graduating from middle school, then we all went to Killarney for another science meeting and had a week in Prague afterwards! On that trip I had her in charge of the maps- she'd lead us around and through the airport as well, just to learn how to travel and to show her that she could do it- what a blast that was!! Now she's 22, and just as together and successful figuring out her life as she was back then. Trips and travel always stay with you! Surely she's not in Italy too?!
Luce- so he suggests two probiotic doses a day? I would guess that means morning and night and that you would take it together with or before the Abemaciclib- the immune stimulation requires dendritic cells drift through the gut and be stimulated by interaction with the bifido bacteria.
I did order a bottle of your bifido- I'm going to take it once a day for a month and see if it does anything to my neutrophil counts and to my energy levels.
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Cure-ious
Let me know if the 5-strain supplement does improve your neutrophil count! I am not having those kind of blood tests but am of course interested in any possible effects.
The oncologist who prescribed the abemaciclib (I only started it today) is a different doctor from the one who recommended the probiotics months ago. I am no longer under the care of the one who recommended the probiotiocs, and my current oncologist has no opinion as to their dosing. Hence seeking advice on the forum. Thanks for yours!
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Cure-ious
It'll last you a lot longer than a month if dosed once a day. While it's very expensive, it is a powder, so the total volume is much more than in, say, a bottle of 30 capsules. I'm not advertising it--I am always interested in and open to a less-pricey alternative, and may try Zarovka's, especially since it seems to have all the pertinent strains--I'm just pointing out that the cost isn't all that outrageous for what you get. The small bottle lasts 1 1/2 to two months if one takes an adult scoop twice a day. And as for the concern about too much of a good thing someone had: I am not sure but I think I read that that doesn't happen with gut bacteria, a bifidum overgrowth. Even at high-level supplementation, It'll only make up a certain ratio of your total gut flora. Can anyone confirm that?
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Luce I think you are correct, its why you have to keep taking probiotics,for the most part they just pass through you without reseeding the gut flora, altho I am not sure why that is so hard to accomplish?, given how fast gut bacteria content can change quickly following a change of diet...
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Just popping in to say hello before going to sleep. I want to get caught up on our Verzenio thread. I take one pill tommorow morning and that completes my first seven days. Like so many have already posted, I do deal with nausea but it is manageable. Today I had my first suprise diarrea attack and I do mean attack. If I had been at work I would have died. My point is that side effects are not at all what I expected. I believe I will do very well on this treatment. Love and Good Night Ladies......Jenny
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Spiced- The company says that the GI problems abate after a few cycles, so please let us know if it gets better as you go along!! We have high hopes for this drug!!
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I read recently that it is recommended that loperamide (Imodium) be taken especially for the first 28 days of one's abemaciclib treatment, to prevent severe diarrhea. And that once the body adapts, the loperamide can possibly be tapered off. I can't find the exact place I read this, but in the source linked below it says for the ESMO 2016 abemaciclib trial that "Patients received prophylactic loperamide concomitantly with abemaciclib."
https://medi-paper.com/esmo-2016-breast-cancer-pal...
I am following this thread, and fascinated. Cure-ious, thank you for the links. I have put them in my notebook. I'm pleased that I can add abemaciclib, possibly with Keytruda, to my list of future treatments.
Z, oh my, your daughter is one amazing eleven-year-old. Why does she have to access your port? No port-trained nurses where you are going?
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Z -
I asked my wife's MO today about this trial at UCSF. Seems it is not ready yet but will be soon. The MO was not extremely enthusiastic about it though, since this is a immuno treatment for ER+ patients.
My wife recently progressed on Halaven. Her MO suggested her to move to Abemaciclib + Faslodex combo, assuming insurance approves it. Although she progressed on Ibrance + Letrozole before, we were told that a CDK4/6 combo with Faslodex can still work.
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Shetland - The nurses are pretty amazing and trained in ports, but we're just not sure they use this particular port in Japan. To be sure, I am bringing the needle and the tubing with us and we're learning how to start it. Or rather, DD will learn how to start it. I literally blank out at the thought of stabbing myself with anything pointy that might produce blood. First lesson went well yesterday.
LMWL - I am happy to hear from you, although sorry about the progression. Knowing the team that you have, it's good to hear they are suggesting abemaciclib and faslodex. I also progressed on ibrance and letrozol. I hope that you hang out here and let us know how abemaciclib goes. It's really important that we gain some collective experience with this new drug.
Jenny - We're hanging on every word. Please check in periodically with your experience. So glad to find you are doing well, but we want to hear the good the bad and the ugly.
>Z<
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