Abemaciclib Verzenio for Stage IV
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jfl: you haven't had Verzenio yet, have you? I think worth trying, especially since you've had a break since Ibrance, right? If you are adventurous, hydroxycloroquine looks to be synergistic with cdk4/6 inhibition. It inhibits autophagy, so you might want to inhibit mTOR again also. Metformin may. Hydroxycloroquine may also reverse endocrine resistance. There are other drugs that may do that also, but I can't think of them right now.
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JFL: is Verzenio follower by Keytruda after 3-4 months of preloading an option? JFCE trial should be publishing SOMETHING at ASCO. But I know one young woman in a FB group who is doing well on that combo. And she said they were recruiting not too long ago. Or your oncologist could try to source Keytruda from Merck
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jfl: you might also want to look into venetoclax:
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a review about FGFR signaling:https://www.thebreastonline.com/article/S0960-9776(17)30609-4/pdf
apparently about 25% of MBC has FGFR1 amplification, especially in luminal B subtypes- an FGFR-specific thread could help get some more insights about what works for this subtype
there is debate about whether the FGFR amplifications seen in MBC are sufficiently high enough to respond to the FGFR inhibitor drugs, and some of them apparently (lucitanib, dovitanib) do not have as bad SEs, and because the SEs are due to to the drug effectively hitting its target, they think those drugs may not be powerful enough.
a subset of these cancers also have PI3KCA mutations, so for those a combo therapy might work
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15% of breast cancers have this mutation, but ctDNA analysis found a higher number (41%) of patients progressing on CDK4,6 inhibitor (IF) therapy have FGFR1 amplifications- yikes!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435685/
they argue for that a 3-way combo is needed for these tumors:
FGFR1 inhibitor:CDK4,6 inhibitor: Faslodex
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these cancers can also be senstive to MET inhibitors like Crizotinib, and may also, as Luce suggests, be inherently more sensitive to immunotherapy.
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cure_ious: you asked a few days ago what might be next for me. I was too tired to reply;constant hotflashes are ruining my quality of sleep and life. Xeloda gets mentioned by my oncologist but I hate the idea of chemo. I had terrible skin peeling on low dose chemo. Also, I am both lobular and ductal, and lobular may not respond well to chemo.
A few months ago, after reading something that suggested rapid resistance (I think; can’t find it now, or remember what exactly it was), i asked my oncologist about PI3k mutation and response to endocrine therapy and he did not see any conflict. Not that I’m considering it; I’m already suicidal from chemo-induced menopause. But I’ve lease remind me what you were referring to when you said that monotherapy might have been the way to go given my PI3k mutation. Thanks!
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Luce, I don't recall right now, but let's think about what alternatives you do have, should the Abemaciclib stop working. Remind me what you do know about your cancer- you have a PI3KCA mutation? why wouldn't they suggest Alpelisib, which should be FDA approved soon?
And there is the MORPHEUS trial, I like that one a lot for once the cancer has become endocrine-resistant; there you can get immunotherapy (Atezo, which is the strongest of the checkpoints) in a combo with entinostat (HDAC inhibitor) or ipanisertib (PI3K inhibitor)- plus, if it doesn't work, or following progression, they have another combo to try that gives you Atezo with Avastin and Faslodex. The Avastin opens up the cancer blood sources to the immunotherapy, and is added specifically in the hope/expectation that it will make MBC responsive to immunotherapy. I know its so hard when you go from trial to trial, but that one sounds hopeful.
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kattysmith, I wonder if you have any more information now about your cancer that might suggest why you are responding to immunotherapy?!!
For example, do you have high IDO1 expression, or FGFR amplification, or PI3KCA mutation, etc? High PDL1 expression or high tumor mutation burden? CDK12 mutation?
And in general, for those few lucky ones who respond to immunotherapy, they generally get a long time on treatment, or more accurately off treatment, since sometimes they can stop the treatment and the patient is on nothing until progression (because your immune system is engaged and doing the work itself).
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cure_ious: thanks for your effort and advice. I'm aware of those options but not open to anything involving further endocrine therapy. Menopause from chemo is bad enough for me; life completely without estrogen not worth living.
The mTOR and PI3k inhibitors just don't work for long. And I don't like their side effects. Sure, my oncologist has suggested them.
I don't think I could choose which Morpheus arm I want to be in, and some involve endocrine suppression, I seem to remember. I'll look it up again and ask my other oncologist (who is at providence, the institution that runs it) about it, though. Thanks for reminder! But I have a friend who is an oncology NP there and the only responses they had had with any type of immunotherapy last time I asked her a few months ago weren TNBC.
(Yep, just checked: one could be ”randomized to Fulvestrant.”
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how do these trials work in phase 1b/2? I guess you would know what you are getting, isn't that right? Can we tell them up front that we won't stay in the trial unless we are treated with what we prefer (in your case, no faslodex-containing arm)? I haven't done a trial yet, so I could be wrong, but it seems unlikely that the trial participants would stay if they weren't getting what they wanted through the trial.
So you'd prefer to go with Halaven than any of the targeted drugs or immuno combos? because of the fewer side effects? there are folks on Alpelisib or Alisertib who have been on for 3 years, so its not always short-term responses. Of course there are people on chemo for years as well, so just would like to know how you make that decision
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Luce and Cure-ious, thank you for all of the information! I am going to go through this and see if there is anything that could be used in the future. There are some new drugs and new concepts I see in your posts. Very exciting. My MO did mention Keytruda as well but I don't know in what context/combo. I will have a chance to ask about all the various treatment options tomorrow. I have Luminal B, HER2 equivocal cancer with CCND1 amplification (Ibrance target), PI3K N345K mutation, FGFR1 amplification, ERSI mutation and many others. One unknown with my PI3K mutation is that it is at the N345K genetic location which is not the common location and is not as favorable in some respects nor as responsive to certain treatments.
Luce, for what it is worth, Xeloda has been my "favorite" drug to date and I would take it over any targeted therapy or hormone therapy I have tried. Most effective with most tolerable side effects. It is technically a "chemo" but is very targeted. It is an inactive pill form of 5-FU when swallowed that specifically activates in the tumors via an enzyme more prevalent in tumors. Limited collateral damage and higher efficacy. I had moderate hand-foot syndrome but really no other major side effects on Xeloda.
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JFL, I think you and I have a lot of common Mutations. I also have CCND1, P13KA and FGFR1 (and a few other FGF mutations). I am sorry to hear about erdafitinib. Thanks for keeping us updated on your trial and wish you good luck on your next treatment plan.
Cure-ious, it does seem like a good idea to start a thread about FGFR status considering that 41% of the people who progress on CDK4/6 tend to have it. Sounds like something that should be the next target after Ibrance as a first line.
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Hello -- I wonder if I might jump in here to ask questions about tumor testing since there is so much knowledge.
My history..IDC found In r breast July 2017. I had been in a major clinical depression for two yrs prior and my Mom had just passed two months before my mammogram. I was inmmediately sent to a surgeon who had no bed-side manner, in 15 min. decided I needed a double mass (only 1 had tumor) and went on to Schule the operation for the following 2 weeks after a series of tests. She set up radiation consultations, plastic surgery concultaions all within 2 weeks of my diagnoses. I could not handle that pressure. I had not even saw an ONC yet. So, first visit to ONC I explained my situation and asked if I had time to work on my depression. (I was 63, live alone, semi recluse and knew that I could not do it at this time)
ONC said you have time. ANd put me on
Arimidex (anastrozole) for six months. At end of six mos. My nurse Prac ordered another sonogram with showed the tumor had grown 1/2 a CM. I did not know the impt of small growth. And Nurse just ordered another 6mos of
Arimidex (anastrozole) (Trying to defend my ignorance, the Nurse Prac. called it staging, had she said straight out, we need to see if the meds are working, I would have understood.)Well, 11 mos from diagnosis my leg started hurting, my ONC took over and ordered CT's bone scans and bon e density. So in 11 mos. I went from stage 2 with just one lump to Stage 4.( there are 4 areas on my skeleton, and very small spots on my lungs too small for PET) ONC ordered Xgeva, Ibrance and FUl injections. Apparently these worked for the first couple of months and then stopped. I spent a total off 4 months on sec. TX
Another tumor developed in my breast, not solid, cribform and the dang thing started to come out of my breast to my aureole, ONC said you're progressing we must get you to another treatment as the ONC has stopped working.
Meantime, my ONC retired, and I had a 4 week wait to see her replacement. Meanwhile small nodules kept growing from by new tumor to my skin. I now have typical cauliflower shaped cancer on my skin. It's ugly and crusty. Of course everyone is worrying about ulcerating. So far it is not.
So, middle of Jan. second biopsy to see if I was still E and P pos and Her-. I am, no change. I was given a choice between Zeloda or low dose taxol IV for 3mos. To stop the skin mets. I just finished #8. of low dose Toxal. No scan yet but, ONc thinks its working because pain in skeleton is gone and I now have no problem with walking, cane's packed away. It's also obvious to the the naked eye that the 1st tumor is shrinking and much less hard. But the nodules are still there. By taking pics it looks like growth has stopped,not sure, but they are not getting smaller. (And of course ONC is now talking about staying on Taxol, if it's working, Standard of Care.. Well, lost my temper a bit on that. That is not how this 3mos treatment was explained to me. So there's that issue to sort out.
Gosh, had chemo today this is steroid talking but I wanted to make sure that I have given enough info to ask the one question that I need an answer to which is...…..
My 1st ONC talked about Found. One testing (before she retired )as has my Nurse Prac. Well, three weeks ago when I asked my current ONC if samples had been sent in yet, he said NO, and would not order the test.
His reasoning is----I've only been on three lines of treatment, there has not been enough time for mutations to develop. I read all the posts on the net about the testing but understand little. In your opinion, is this info correct? Is It too soon for mutations?
Anyone who's read all of this you're currently in my thoughts and prayers. I thank you from my heart
Snooky
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jfl: thanksfor the thumbs-up on xeloda! while I have a feeling that Verzenio is my xeloda—very tolerable—I understand that xeloda is unlike other chemos, which is why my oncologist keeps mentioning it. I may consider very low dose (600mg twice a day; 1week on/one week off) but am concerned that median PFS is four months! My onc says that's because only a few people do very well on it, sometimes for years.
Major muchreported side effect in the xeloda groups I've been lurking in is huge weight gain! Yikes.
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Snooky, my oncologist has not ordered any kind of testing and I've had Mets for 7 years. I don't know if the way it's normally done, but it seems as long as a treatment is working you want to stick with it. Same with the taxol. If it's still working for you, it's normal to stay on it, maybe with breaks if there's to much toxiciy or intolerable side effects. Unfortunately most of us will be on some kind of treatment forever so it's best not to use them up too quickly and then be left with nothing.
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luce for what it's worth, I share the same enthusiasm about Xeloda as JFL. It has been my favorite treatment to date and it's with great sadness that I have to switch treatment due to progression after many months.
As far as your fear of gaining weight, all you have to do is to time your meals accurately every 12 hours, since it's a good idea to take it with food. I have discovered that even eating some fruit in the morning is sufficient to buffer the drug.
The dose you’re considering is extremely low, thus I doubt you will suffer from any major SE. I was on 2000 7/7 and I had only minor SE
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Miao: good to know you are seconding x.
My oncologist did not suggest that dose; I did after some research.
Here's s problem, then, if it needs to be taken with food: I only have a 6-8 hour eating window every day.
Still set on trying other things first, like anthelmintics
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HLB--- I know, I know that you're right about staying with the taxol if it' working. I was just so terrified going into chemo. Took all my resources to force myself to do it. Kept saying 9 times, 9 times, and then when the ONC gave me different info. My mind just did not process it yet. I'm getting there. But I do realize that you're right. Thank you for your time in answering.
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luce...it’s funny you mentioned anthelmintics because I too believe those and the antifungals are the key to controlling this disease. But all the good functional doctors in Manhattan—that I used to see— have died and I don’t trust the new ones on the scene.
Are you going to do the protocol on your own or under supervision?
I have been rotating the intake of artemisinin, chaga tea, and turkey tails in addition to an antifungal diet. The observable results? My hair was white and now is gray and my blood sugar is below 100 I was diabetic. I would like to use the heavy antifungal artillery but I'm afraid those medications are also invasive and toxic to the system as chemotherapy., and there are no clinical trials in that direction available at MSK...I checked months ago with my MO...he looked at me as if I were from Mars.
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I’d go it sort-of alone but tell my oncologist. They are using mebendazole at UC San Diego’s personalized oncology program, so it’s becoming more mainstream. I’m not an expert yet but, yes, anthelmintics work much like 5FU and taxol chemo: interrupt microtubules, for example.
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apparently, the amino acid leucine is implicated in tamoxifen resistance:
https://www.medicalnewstoday.com/articles/325007.php
(I know pretty much any amino acid is somehow implicated in cancer, but since we mentioned endocrine resistance yesterday. Researchers were “surprised.” Maybe worth cutting down on animal products IF one is trying to prolong endocrine therapy.
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Luce, I've been following your discussions with Cure-ious regarding some of these 'unusual' therapies.
As a retired pharmacist, I asked to go back on gabapentin in January (it was prescribed after my spine surgery to mitigate potential nerve pain: I had done a taper to discontinue it in October) because night sweats were waking me up 5-6 times. A 300mg capsule qhs cut that number in half so we doubled the dose and now I sleep well until dawn. Have you tried any of that for your quality of life?
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yes, thanks,I’ve tried gabapentin but wasn’t comfortable going above 300mg. I know some people have to go up to 900 to control hot flashes. I discontinued when 300 wasn’t effective.
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Luce, I did gain a little bit of weight (8-10 pounds or so) when I started Xeloda. For me, I always thought it was the mini "estrogen surge" from going off aromasin and faslodex that caused the weight gain rather than the Xeloda. The body tries to store fat like it is going out of style. I had the same small weight gain when I went off tamoxifen years ago. In both cases, it took about 9 months for the weight to come off. For those coming from other chemos, they may gain weight because the other more harsh chemos cause loss of appetite, nausea and/or premature fullness, whereas xeloda does not necessarily cause that. I honestly don't think there is anything about the Xeloda itself that would cause weight gain - it just doesn't cause weight loss or difficulty keeping weight on.
I had my MO appointment today and he put me on tamoxifen. I started today. Threw me for a curve ball but who knows. It didn't "cure" me when I took it for early stage BC but did keep me clear for 8 years - 4ish on tamoxifen and 4 thereafter. I may get a port in a few days and add navelbine chemo next week. His other option would be to add testosterone to the tamoxifen. A few others at my treatment center are doing that and it is working well for one of those persons. I haven't heard about testosterone ever. My MO said it used to be used long ago and was forgotten over the years. He also recommended consulting with my IR about a potential 2nd Y90.
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jfl: I've heard of use of progesterone. and of testosterone depletion/ blocking (in hopes of reactivating the thymus gland, for one). But not of adding it. Interesting.)
Tamoxifen seems to have benefits besides being a SERM. For example, it lowers IGF-1, supposedly . And inhibits P13k. It would still be my oncologist's first choice of antiestrogen for me if I were open to antiestrogens. (I'm not.)
I hope tamoxifen comes through for you again! If you are taking curcumin, I would stop that:
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Several years ago I dispensed methyl testosterone to an older woman for breast cancer treatment. There are so many other options out there now, I don’t know how commonly it is utilized these days...
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Luce, thanks for the reminder about curcumin. Will pack away my turmeric for now! I do take it daily.
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Thinking about you JFL—as I 'm sitting here and wait to get the bloodwork done before meeting my oncologist—and wishing you a long lasting and great outcome from your new treatment,
After reading the statistics on the testosterone treatment trial, I'm thinking of suggesting it to my MO. We'll see what he says.....
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Anyone else notice a wave of anxiety shortly after taking a dose of Verzenio?
I'm a week into month #2. I don't typically have regular anxiety. I just realized this morning that this daily post-dosing shaky time is proving consistent enough that I should start tracking it, and try to conjure up some strategies for managing it.
Anyone?
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