Abemaciclib Verzenio for Stage IV
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Namaste from India!
My mother was diagnosed with de-novo metastatic breast cancer with bone/liver mets in November'17. Doctor recommended her to participate in the MONARCH 3 trial of abemaciclib (150mg) and letrozole as first line therapy. Today the first cycle got over but so far we have been really bothered with the frequent and stressful diarrhoea. It has really been unpredictable and bothersome so far. She has been on frequent loperamide doses but it has really been of little help. I think Lilly has underplayed the diarrhoea angle as I feel her immunity is really deteriorating. While I have been reading that things get better after first cycle, we are just hoping that things improve because mom has been really stressed out.
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LMWL- Thanks for posting the MORPHEUS trial- it has different arms that include Atezo (immunotherapy) with Akt inhibitor, BRAF inhibitor, or fulvestrant/AI, and I like that there is a triplet combo one can go onto if one does not respond, or has too many SEs, in the trial arm they are assigned. Is already recruiting in some locations, and slated to come to Memorial Sloan Kettering, UCSF, and UCLA, etc
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Alright then Z,
I think I am doing pretty good so far. The nausea has calmed down a bit. I know that when I have extreme anxiety that my stomach is always upset. I either have no anxiety or extreme but that is another topic. Before the mets I was doing so so well....no IBS and was Isleeping through the night. Miy counselor said that I am probably in shock and that is natural considering my issues with a mental health diagnosis. So it would be normal to have anxiety, ptsd, etc. and she said I am the strongest woman she has ever helped and that we will get through this too. ::) If you knew my story that is a big assurance.
I've had one episode of explosive diarrhea. It was yesterday and I took loperamide and I am okay now. The problem is I have no clue what I will do when I go back to wrok on Tuesday. I would never make it the bathroom. I sat on a double folded thick towel the rest of the day. If any of you have ideas please let me know. I have to have a solution to the diarrhea before it happens.
I wonder about some other things that y'all might have some knowledge about:
What do you eat for breakfast? I am not getting any protien w/ bkfst right now so I thougt I would add a half of a scoop of protien powder with water and drink that? It is vegan because I am lactose intolerant. I like to meal prep on the weekends so that I have the best nutrition possible.
How do I fix my sleep? I take ambien and it works like a charm until now. I exercise 30 minutes a day and get good cardio. I keep my room dark, I have an aromatherpy diffuser that I put lavender eo in.I have tried the Calm app and it really helps me go to sleep but I wake up every two hours and I eat. and that is unhelpful.
I forgot to tell you that I now have a sore inside of my mouth and of course extreme dry mouth.
Thank you for listening to me and now I am going to catch up reading your messages for the last few days so that I will be up to date with whats going on!
Love, Jenny
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Shock panic and trauma are pretty the norm after the initial diagnosis and then we get to go through it all again with each progression. Ah MBC, the gift that keeps giving. Pretty much all MBC patients exhibit PTSD signs. My point is that don't let the shock etc itself freak you out and make you more stressed. What's not to be stressed about ... you have crazy growths trying to disable primary organs. At the same time we all eventually get periods of respite from the panic. I hope that being on a cutting edge drug that is best in class may give you some confidence and peace.
They have diapers for that situation. Losing control of one's bowels is common in very late stages of MBC, yet the tougher among us go to wedding etc. wearing diapers. I am going to be hiding in a closet at that point, but Depends and a clean up kit may be one solution to get you through work. As Cure-ious points out, the data suggests that the diarrhea resolves with time. Your gut biome takes time to adjust to this new agent but it appears that it eventually does. I wish I had some time to study what abemaciclib might actually be doing in the gut.
You may be doing the best you can on your own with sleep. Those are all the standard tricks. You might consider asking for referral to a palliative care doctor. It's a specialty that looks at treating these side effects of treatment and they may have prescription meds. However, I am seeing evidence of high levels of stress. The fear and panic may be something you just have to work through. Your counselor may be the best avenue to a good night sleep. I like that lady.
Another reason to see a palliative care doctor is the dry mouth. I don't like dry mouth because I think it is the tip of the iceberg of a larger systemic problem. I had it myself with ultimately serious consequence. It's basically a sign of systemic dehydration. In my cause the cause was very different so I can't help you sleuth the source of this. I am wondering about a drug interaction or supplement that isn't doing what you think it is.
You are doing great with so many pieces slightly out of place. I would start with building some confidence that you are on the track ... because you are. Once you see path forward leading in the right direction, some of these issues will become more manageable.
>Z<
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Z, thank you so much. You rock! For the I can wear the diaper and by that time my body should have it figured out. I will check out the palliative care. Jenny
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Spiced life, I work full time and feel for you with the whole work predicament with Abe side effects. I expect to be on Abe sometime in the not too distant future and that is my main concern. I eat yogurt with 2T of flax seed and a banana for breakfast. Flax seed is a good source of protein and can also be added to oatmeal or cereal. That goes for nuts as well. I also sometimes eat a cold cereal called Ezekiel which has a high amount of plant-based "whole" proteins from the sprouted grains it contains.
Z and Cure-ious - I read a disturbing article yesterday about how dietary xenoestrogens, including genistien from soy, can directly counteract the mechanism of action of Ibrance/Femara, in very small amounts. Have you heard about this?!
https://medicalxpress.com/news/2018-01-estrogen-mimicking-compounds-foods-effectiveness-breast.html
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JFL- I posted to this on another thread, basically our bodies are highly depleted of estrogen, and so we should avoid any estrogen-like compounds, which are found in plants like soy (no soy supplements for us) and are also in plastic wraps, microwaving plastic, etc is not a good idea. However, keep in mind that these drugs have huge effects in clinical trials, and the individuals in these trials are eating normal diets like the rest of us. Stay away from environmental estrogens as much as possible, but I think this story is over-blown...
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hmm. it's a theoretical benchtop study but it does make sense. we know that ibrance doesn't work as single agent. if the hormone suppression is not working because estrogen is replaced by xenoestrogens then ibrance won't work. the relevance goes beyond letrozol ibrance since keeping estrogen low is a key piece of MBC treatment generally.
that said, xenoestrogens are hard to avoid. possible sources go way beyond soy. it seems you already eat very well. i could clean up my act a bit.
thanks for the reminder.
>Z<
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What is so deflating about the article is that it is just another reminder that we have limited control over some of the environmental factors. I do try to stay away from BPA, plastics, pots and pans with coating, etc, but there is no way to fully avoid all these potential pitfalls. I also stopped consuming the isolated soy isoflavones and other potent soy-derived supplements/products after I was originally diagnosed 11 years ago but do still eat soy foods such as miso, tofu and edamame.
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I am on week 2 of Verzenio. Diarrhea, but not terrible. Depression due to progression.
Ibrance treated me well for 2 years. Good luck to all those on or starting Verzenio. My Oncologist told me that a recent study said it was very good for bone mets so that is my hope.
- Jane
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Jane - did you switch to verzenio right after Ibrance failed and are you taking it with letrozole or faslodex ? Did you have any trouble getting it approved from insurance
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I have been on abemaciclib and Faslodex for 14 cycles and have done very well. I have had a positive response( between 55-75 %) in shrinkage of liver lesions. This has been my experience with abemaciclib. I have never had 'explosive' diarrhea, but have had some bouts of diarrhea which I have been able to control with Imodium. There is a fine line between taking enough and taking too much which leads to rock hard constipation!! Yes, your body does become accustomed to the drug, and the diarrhea episodes do become less. I experience very dry mouth and changes in taste. The only thing I have found to counteract that is the various rinses and throat sprays. I have discussed this at all my MO appts with her and the clinical nurse who is fantastic with coming up with various ways to counteract it. Not much helps. I am going for acupuncture for the dry mouth and neuropathy (only on the feet) which I have also also developed. I did have a mouth sore and was prescribed a cream that is usually used topically but which I used orally. I don't have the name as I am away from home. It worked quickly, but the sore was already starting to heal. I am also experiencing thinning of my hair. Not sure which drug is contributing to this. I take Nexium daily to counteract heartburn and a probiotic very day. My routine is Nexium, an ordinary breakfast (cereal, corn muffins, eggs, yoghurt) , wait an hour and then take abemaciclib. I wait An hour later before I eat or drink anything again. I don't follow a ritual in timing of doses. I’m actually very casual about it. There are times I don’t get to take the first dose until early afternoon. I take the second dose after 11pm. I check with clinical nurse before adding anything (vitamins, supplements) to my routine. She always checks with the sponsor before giving me the ok. I was never told to wear gloves when handling the pills. I do keep them separate from others I take. When I had to have a minor surgical procedure she checked with them to learn when and for how long I needed to hold the drug. Hope my experience may help some of you as you start this journey. My dosage is 100 msg twice a day
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MZR. This is very interesting and helpful and I speak on behalf of many when I thank you for taking the time to detail your experience. Please hang around and keep us updated.
Technically you are on a dose reduction for abemaciclib in combination therapy. Were you ever on 150mg 2X per day?
>Z<
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Constantine has a good facebook page if anyone would like more of his writing. He is good.
>Z<
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Yes, Z, I started abemaciclib on the trial at 150mg 2X a day as well as the drug LY3023414 st the same dosage. I developed a horrible rash , and the dosage for both drugs was reduced. The rash came back with a vengeance, and it was thought that LY3023414 was the culprit. That drug was eliminated , and I continued with the lower dose of the abemaciclib.
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Interesting. Do you have any news on how that trial is doing. It is a drag that LY3023414 gave you a rash. Promising drug. But It is great that you are responding well to the lower dose of abemaciclib.
>Z<
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So my tumor tested negative for PD-L1 expression and also negative for microsatellite instability. Could there still be any possible benefit in adding Keytruda or another immunotherapy drug to the abemaciclib i am taking? Thanks for any insights into this.
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Luce - That is a good question. The relationship between PDL-1/PD-1 expression and response to anti-PD-1/PD-L1 agents is not as high as one would expect. I know a lot of people respond with out PDL-1 expression in their tumors. I believe it is partly because the inhibitors can interfere with receptors on the cells of the immune system as well as the tumor and partly because PDL-1 expression is transient and can depend on cytokines in the tumor micro-environment. The link previous in this paragraph gets into details.
The relationship between low TMB and weak response PDL-1 inhibitors is stronger. When outcomes from anti-PD-1/PD-L1 monotherapy was analyzed (N = 102 patients) they found a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders vs. non-responders treated with anti-PD-1/PD-L1 monotherapy was 18.0 vs. 5.0 mutations/mb (P < 0.0001).
Benefit from dual checkpoint blockade (anti-CTLA4/anti-PD-1/PD-L1 combinations) did not show a similarly strong dependence on TMB. It's not clear whether anti-CTLA4 inhibition alone works better a high TMB but there are trials combining anti-CTLA4/anti-PD-1/PD-L1 and since there are FDA approved drugs which act on both pathways, it would seem that one could prescribe the combined protocol off label.
I see that you posted your question on the Abemaciclib thread on Inspire. The people who really understand checkpoint inhibition hang out on a thread dedicated to PDL-1 checkpoint inhibitors... try reposting there. I am interested in the response you get.
https://www.inspire.com/fighterm/journal/pd1-pd-l1...
>Z<
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Thank you, Zarovka!
I guess one could try adding Keytruda to abemaciclib since adding it didn't seem to cause any additional side effects. I would like to find a combination that actually has a high(er) chance of actually working, though.
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I am starting Abemaciclib 150 mg. twice a day today along with Faslodex shots every month. Taken off Ibrance 150 mg. had internal bleeding in February and early December. Other months were on 75 mg. Ibrance with no bleeding. Actually looking forward to the drug as my oncologist is quite optimistic for a lessening of progression of metastatic breast cancer.
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Posting the abstract from an article I linked to earlier on PDL-1 expression in tumors and immune cells. Explains why PDL-1 expression on tumor cells is not closely correlated with a response to checkpoint inhibitors.
Antibody blockade of programmed death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy. Using CRISPR/Cas9-induced loss-of-function approaches and overexpression gain-of-function techniques, we confirmed that PD-L1 on tumor cells is key to promoting tumor escape. In addition, the capacity of PD-L1 to suppress antitumor responses was inversely proportional to tumor cell antigenicity. PD-L1 expression on host cells, particularly tumor-associated macrophages (TAM), was also important for tumor immune escape. We demonstrated that induction of PD-L1 on tumor cells was IFNγ-dependent and transient, but PD-L1 induction on TAMs was of greater magnitude, only partially IFNγ dependent, and was stable over time. Thus, PD-L1 expression on either tumor cells or host immune cells could lead to tumor escape from immune control, indicating that total PD-L1 expression in the immediate tumor microenvironment may represent a more accurate biomarker for predicting response to PD-1/PD-L1 blockade therapy, compared with monitoring PD-L1 expression on tumor cells alone. Cancer Immunol Res; 5(2); 106–17. ©2017 AACR.
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Wow -- a lot to get caught up with here! Sorry I've been away. We're selling our house and have been busy cleaning things up for potential buyers.
Zarovka: I asked my MO about the rebound effect. She gave me a bit of a perplexed look. She's not heard of it. She told me something else that was really interesting and relevant -- and I completely forgot. This happens when I don't write things down. As soon as I remember, I'll post it.
I've been considering seeing a nutritionist to figure out if there's anything I can do to help with gut issues and make sure I'm eating properly. I'm kind of bothered by the fact that Eli Lilly doesn't know what exactly causes diarrhea. I was never warned what not to eat. I had to figure it out myself. Might be a good idea to keep a detailed food diary.
I think a couple people have brought up mouth sores. I just use Biotene. Worked great for chemo and works now, too.
mzr119: I'm also taking LY3023414. I got a bad rash (like hives) but chalked it up to soap. The rash went away. It comes back every now and then, mostly on my hands and arms, but it's pretty minor. The most serious side effect was a drop in my phosphorus levels. They reduced my dosage and gave me a prescription for Phospha.
Really, overall, I'm doing great. I feel so fortunate to be feeling this well, given the diagnosis. A year ago at this time, I had a pleural effusion, a tumor pressing up against a heart valve, a broken rib and was in constant pain. Now, all lesions and tumors have shrunk or disappeared and my CA153 has gone from 800+ to 60. I have a scan in three weeks and will let y'all know how that goes.
And, Z, promise to try remember that comment from my MO
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Mazie - Thanks for checking in. I strongly encourage you to get help from a specialist like a nutritionist on the gut issue. Oncologists and pharaceutical companies have no training or interest in diet and gut health. Absolutely critical yet not what they do. Interested as always in what you learn.
I am waiting to see a paper before I believe the rebound effect.
Mostly I an thrilled to find you doing so well.
Best,
>KNC<
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My Onc told me that Verzenio wouldn't work because Femara/iBrance didn't work for me. Aren't these drugs in different drug classes? She did say she had to look into this, but I was surprised to hear it given that many of you are on it and some of yo had no success with the combo Femara/iBrance.
I'm beginning to wonder if I should look for another Onc..
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disappointed to report that on day six on abemaciclib--today--like clockwork, explosive and watery diarrhea started. very unpleasant. i'll probably opt for a dose reduction over immodium. i am not comfortable with opioids of any kind. and i'll never ingest anything the color of pepto-bismol.
i'm not really sure why i am on abemaciclib anyway, since my life-expectancy is less than the response-time.
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booboo - abemaciclib is the same class of drug as ibrance - it's a CDK 4/6 inhibitor. but there are a lot of reasons to keep it as an option on the table. ibrance doesn't work if the hormone suppression is not work, so you don't know whether letrozol failed or ibrance failed. abemaciclib was effective as a single agent and therefore not necessary dependent on hormone suppress. you might try abemaciclib with faslodex or alone. Or you might try an entirely different class of drug for now if you need to be confident that you will control the cancer now. It doesn't take abemaciclib off the table for later.
Luce - Rats. Your choice whether to soldier through the side effects or not. Very personal business these decisions. Always here to chat. Hugs.
>Z<
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Luce: are you eating raw vegetables?
Since I'm on a three-drug combo, I don't know what drug is doing what, but I had a response within a month -- pleural effusion cleared up. I encourage you to hang in there! It should get better.
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mazie: thanks for your reply! (zarovka: ditto!) no raw vegetables today.
so glad your drugs took care of your effusion; i currently have a 2+ liter effusion on my right and did before on my left (that one was fixed with a pleurodesis a year ago), so i know how unpleasant they are. i suspect yours responded to the faslodex. at least that's what my oncologist told me, that estrogen blockers would probably help. i am using abemaciclib as monotherapy, though, and have read it takes between 3.7 and 7 months to respond!
update: i just asked my oncologist what likely worked on your effusion, and he said probably the targeted therapy. since i don't want endocrine therapy, it won't work for me.
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Luce: Just curious why you don't want endocrine therapy?
And, add dried fruit to the list of foods not to eat. Sigh. That one should have been obvious. I took a bag of trail mix with me to run errands today. Won't be doing that again.
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Mazie: Tried endocrine therapy and didn't tolerate it. I value quality of life over quantity with joint pains and fatigue. Frankly, I think it's barbaric, blocking a woman's body's estrogen receptors (for the most part). I am very angry that after 40 years of Tamoxifen, there isn't any endocrine therapy yet that only blocks the cancer's receptors.
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