I tried to show my oncologist some research from Dana Farber that found that the reason CDK4/6 inhibitors develop resistance is NOT because of mutations but because of another response that overcomes the treatment. The research suggests that after a "vacation" of 7 weeks , Ibrance becomes effective again. I know some people on here have tried that. (My oncologist refused to look at the research and just said, "mutation." And "it's not standard of care yet.") I am running through treatments too fast. Ibrance was easy for me and made me NEAD (along with fulvestrant -- probably more the fulvestrant) for a couple of years.
I would like to retry Ibrance, after 2 years off it. Has anyone done this? Did it work for you? What made your oncologist try this? Because they were at Dana Farber?
Thanks, Chris
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Thanks! I did go to Verzenio after Ibrance failed, but I didn't have a vacation. Maybe I didn't need it because after Ibrance, I was on an oral SERD for a year. Also confirms what I have been telling my oncologist to no avail: that CDK4/6 inhibitors fail not because of a mutation but because of the amping up of the production of CDK/6 by cancer cells.
Excellent review! Unfortunately, we'll have to wait for the medical studies to have any definitive answer. It also may be the case that only some peopleprofit from a second round of the CDK4/6 inhibitor but, until medical researchers start to classify their subjects into groups by specific criteria such as age, blood pressure, enzyme levels or what have you, we are going to remain not knowing why...
My experience with trying to get oncologists to read current research has also resulted in a similar reply, "It's not in our practice guidelines." All physicians seem to worry much more about being sued than the chance of actually doing their patients some good...
She has taken several articles from me before,, and we have discussed them and their relevance to my treatment. This time she refused to look. She just got promoted so I guess she doesn't need to learn anything or has less time.
My guess is that your oncologist may be resisting the idea because Pfizer may not provide the patient assistance for situations not considered “standard of care.” The cost without their program is exorbitant.
It might be worth checking directly with Pfizer. I wish you luck with this and hope you keep us posted.
I’ll keep you informed of my similar situation. I am currently being treated with Enhertu which has resulted in shrinkage of two or three small liver tumors. However, my tumor markers keep rising. My oncologist is hoping to zap the liver involvement and possibly return me to hormone therapy. So I would hopefully move on to an earlier therapy and see how that goes.
It’s a lot of hope and prayers, isn’t it? God bless you, Tammy! 🙏🏻🙏🏻💗💗
Yes, I had FoundationOne last time I developed resistance (and she supported my going to MSK for a second opinion). It showed only one mutation that suggests no treatment. In fact, they don't even know if this mutation is good (protective) or bad (promotes cancer or fosters resistance).
This time, it is not quite time to change. I have two spots that disappeared from one scan to the next, one that stayed the same, and one that heated up little more. It is still not definitive, not that bad. I am just thinking, thinking. If two spots responded to the treatment and two didn't, does that mean they are different? When it is time to change, I will ask for another genetic test.
She is not obstinate about that; it's just that she won't consider the research that shows that resistance is not always due to mutation.
Good! At least she’s open to the testing. I showed no mutations so that makes me worry that there’s not much they can do if my Ibrance/AI stops working. 😢
Someone else said that -- they were disappointed not to have mutations. I felt the same way when it turned out I had none (or one that doesn't dictate treatment). As I explained before, it took me a while to realize you really really do not want mutations. They complicate treatment. There is just one new treatment for the two most common mutations. They mean the standard treatments will not work. That is not good. If you do not have mutations, you can go on other CDK4/6 inhibitors and SERDs instead of AIs or a different AI. They don't know why, but each seems to work when the others stop. So you have options after Ibrance -- and the possibility of going back on Ibrance after a vacation (which is where this string started).
Thank You!! So good to know!! I’ve just begun this MBC journey (started treatment last July) after 12 years Cancer free. So much has happened and treatments are constantly evolving!!! It’s hard to keep up!!
On your other post, saw my dentist recently. She is at the same place I get cancer treatment, so is particularly knowledgeable. She said I was lucky, because some people get a side effect from meds that is so bad it is painful to swallow. -- Can you see a dentist about this? Also, your oncologist should know (and the nurses in breast oncology, who are often better at side effects).
Thank you! The doctor in the ER referred me to an ENT specialist. I think he was worried it may be cancer. I did send a message to my nurse practitioner and my oncologist. Unfortunately, it’s the weekend and they aren’t particularly interested in reading their email from work. 🤷🏻♀️
I do see my dentist every 6 months and went last month. I didn’t have this awful sore then!! It’s so painful. I’m praying it’s just infected and the antibiotics will take care of it. I’m calling the ENT doc first thing, though!! 🙏🏻
Hi Tammy, I do hope she comes round to your way of thinking. Why not just try for 3 months minimum and see! What’s there to lose??? If A lot- then I understand, if not…. Try 🥹
Why do you say you are running out of treatments- has she told you or are you assuming? I never ask anything meaningful at my app other than cry when I have to change meds. I do know my next line of treatment is taxol and I am so desperate to keep to oral meds, anything other than IV chemo. BTW when I cried when she tried to put me on Taxol in Jan, she let me try vinorelbine instead 😊 so I’m hoping this tactic works again when she starts mentioning ports & IV (fingers crossed) 😉
Crying is not a strategy I have tried with my onc! My cousin who accompanied me to early appointments calls her Dr. ColdFish. I guess I am Dr. ColdPatient.
The way I have learned about my options is that she outlines them and writes them down every time I have to switch. She did that from the beginning: three possible combos before chemo, and she said we are trying to avoid chemo as long as possible because of the effect on QOL (hair loss, nausea, etc.). I have gone through two (fulvestrant and Ibrance; verzenio and abemaciclib, which I am on now, not quite ready to change but it looks like I will have to in the next year). That leaves ribociclib (Kisqali) and exemestane. I gained a year by going on an oral SERD in a clinical trial. The one good thing is that she has been looking for clinical trials for me. Hasn't found anything yet.
Good luck with vinorelbine! It is considered chemo, and the side effects look tough, but Taxol sounds more toxic. You are not supposed to drink coffee with it! That sounds terrible.
I agree! Do taxol as last resort. Too many long term side effects for something that will never get rid of cancer completely. I did it after Piqray. I regret it now. Only worked 6 mo. Yet it will take a year for my hands and feet and hair to recover. Now back to pill named Elacestrant only on this 1 month will see if it works
thank you for bringing up this question. I’ve been on IBrance for about 33 months with two kinds of dosing: 125 mg and now 100…moreover, I’ve switched from the standard 3 weeks on and 1(or 2) weeks off, to the 5 days on and 2 days off without break in order to prevent the extreme neutropenia I was enduring. Now, the tumor markers are rising …and so does the question of what’s next.
I wanted to tell you that Dr. Mary Chamberlain of the Dartmouth Hitchcock hospital in Lebanon NH reassured me back in 2020 that there was a lot of research going on about the reactivation of IBrance. She said it might be possible to make it work again after a “vacation”. Depending on what is revealed in next weeks scans, this may be my next step…to have my Onc consult with her about this possibility.
Twenty years ago I had chemotherapy. I’m not eager to go that route again if there is a chance to delay it, or avoid it for longer.
My best wishes to you. May this next step be the one that many of us can follow in pursuit of long lived health and comfort.
Dana Farber has a second opinion phone number to call. Try calling Dana Farber directly to set up a telephone or online consult. See if you are able to meet with the Oncololgists who conducted the study. Ask them about rechallenging the cancer after an Ibrance vacation. I am familiar with the study you referenced, but I have never heard more about it. Hopefully they will be able to advise.
Actually, it is a series of studies, some with "petri dish" cells. I don't think there has been a definitive trial with humans. That is probably what my onc is waiting for. She is conservative that way.
The link that someone else gave presented a much more complex picture of the pathways to resistance, not the single straightforward one in the Dana Farber piece.
Following.....thanks for sharing the experiences and study in the pipeline. My onc is a protocol only person but has told me many studies are looking at changes in dosing the combos of drugs and even now the finding of the ESR1 mutation and Elasetrant could be combined with the CDK inhibitors.
My oncologist talked about the same thing. When the fulvestrant fails, we will test for ESR1 mutation and go on to Elacestrant if ESR1+. I read many MBC patients do mutate to ESR1. If no ESR1 then Xeloda. Ibrance and Letrozole failed after 16 months. Currently I am in the Monarch 3 trial to see if Fulvestrant and Verzenio will bring additional time after a prior CDK4/6 failure. Unfortunately I don't know if I am getting the Placebo or Verzenio.
I had a blood biopsy after Ibrance and fulvestrant failed. I did not have ESR1, so onto verzenio and anastrozole. Seems to be working somewhat. Not as well as the first treatment. I believe that they say each new treatment works less well, or not as long, as the previous one.
Yes I have heard it said that each subsequent treatment works less well. However I have also seen women not do well on one treatment but do very well on a subsequent treatment. MBC seems to be more of an up and down, back and forth process rather than a straight line. After writing this morning I reviewed the clinical trials on the Dana Farber site, there is so much in the pipeline. Maybe a fresh pair of eyes with a new perspective might have something to offer beyond what you are thinking about. Thanks to video conferencing it is easy to connect with the top cancer centers without travel. I also heard an interesting statistic "people who avail themselves of trials tend to live longer".
Hi, I was just reading through this thread and was intrigued with your statement about video conferencing. I am aware that you can do second opinions in written form without traveling and you can do them in person but not on video conferencing. Have you done video convening for a second opinion? I like the idea of asking spontaneous questions which you can’t do with a written second opinion. Thanks!
Hi HelenWi. I have not done video conferencing for a second opinion. Yes there is the written process for second opinions. The suggestion was offered in the context of inquiring about trials. Given today’s technology it never hurts to ask, especially when they are trying to recruit people for trials. It may be something a provider could accommodate as an exception on a case by case basis. I had a Doctor from my cancer center write me asking for my participation in a trial she was conducting. She followed up the letter with a phone call to me during the recruitment phase of the trial. I felt she may have been open to a video conference call if I asked.
I had read about this 7 week break from Ibrance also and it sounds very intriguing and makes some sense. My oncologist does not use Verzenio so if I need to change treatments from Ibrance, I'm not sure what she would recommend. Also, my insurance prescription plan does not cover Verzenio or any other drug like that except for Ibrance. Not sure why. Anyway, it would be great to get more statistics on this break and see if our doctors would be willing to try it. Good luck to you, sending hugs.
Sounds like it would be good for you. I have just that one article on it, but it looks like there will be more, and maybe a clinical trial. My insurance covers neither Ibrance nor Verzenio sufficiently to make it affordable, so I got both free from the pharmaceutical patient assistance program. Why doesn't your oncologist use Verzenio? The money, or something else?
A clinical trial for that would be great. I get the Ibrance free from the program also as I have Medicare plus a supplemental plan. The insurance company changed their prescription drug company and Ibrance is listed as the only CDK4/6 drug they cover. My oncologist does not use Verzenio because of the issues with diarrhea, at least that is what the nurse practitioner told me.
I had read something, not in-depth, that sometimes after a break, doctors will use a previously used drug again. I would certainly be in favor of that knowing how I reacted to a previous drug.
So I had Ibrance then Xeloda and now a clinical trial (Capivasertib + AZD).
My cousin in France goes to Gustave Roussy cancer institute near Paris and her onc is one of the best in Europe.
She had Ibrance for 2 years, Xeloda (did not work), Afinitor, IV chemo with a clinical trial and back to Ibrance and she got 9 months out of it. Now she is on Abemaciclib.
So I think it’s reasonable/rational to want to try it again. I hope you will ne able to exchange about it with your onc.
Interesting. So she did go back and get more time. Good to hear. (I am on abemaciclib -- Ibrance worked better for me, for 2 years (NEAD) and the side effects were easier, so I am eager to go back. -- If I can get into the patient assistance program again!
What is your trial? I haven't heard of it. How is it going?
Hi Helen,How interesting. I'm also in France. My onc is pretty good and I believe I'm getting the best treatment.
Just in case I needed a second opinion in the future, could I have the name of your cousin's onc- private mp me ? He seems up to date with clinical trials and the different options available.
I read this report a few months ago and showed it to my oncologist as I had just had progression to the liver while in Ibrance/ Letrazole. He said that the guidelines prevent them prescribing CDK 4/6 inhibitors any more once progression has occurred. The funding would not be available.
I asked if I could self-fund and he replied that I could be wasting a lot of money for something that has no sound data behind it. This is true, but I wont be using that money if I die I pointed out.
Unfortunately, unless we go on a clinical trial, there is no room for bending the rules and experimenting. I understand that as no one want to face a law suit if it all goes pear-shaped.
Where are you? There are people on here who go back on Ibrance. They may be at Dana Farber. Certainly, though, we in the US can go to a different CDK4/6 inhibitor. That is actually standard practice. Not sure about the funding but I have qualified to get two different CDK4/6 inhibitors free from the pharmaceuticals that make them.
I'm in the UK. They will not release funding unless there is a strong evidence base behind the decision, and apparently in the case of CDK 4/6 inhibitors, there is not. There have not been enough studies which show sufficient benefit, n terms of survival figures. I could self-fund at £4,000 p/m, but the oncologist was not sure that it would actually be any use. if these drugs have the same mode of action, maybe you fail on one; you fail on all.
I imagine, if the present data does not support cost effective prescribing of an expensive drug, we wont get it. And as I've just gone onto another expensive drug, Piqray, they wont prescribe both. Maybe I should look at the data supporting using an alternative CDK and make a decision about self-funding if this latest treatment fails.
If you are on Piqray, you have the mutation that suggests Piqray is best? Or is that because of the liver?
My oncologist at Columbia and 2nd opinion at MSK both advise trying all three CDK4/6 inhibitors in succession. My main oncologist said it is "just anecdotal," but with her patients it has been working. The MSK oncologist also said there is not good data -- but she meant on any of the CDK4/6 inhibitors; on one, the trials are old, before the other meds were available; on another, it is new so the data aren't in (I forget which is which) and they haven't been tried head to head.
So the UK policy is rational -- but wrong. I am getting some mileage out of Verzenio, not as much as Ibrance. Next up is ribociclib. I would like to re-try Ibrance, and that is what my oncologist said is not standard of care. Yet you can see here that it is working for some people -- haven't heard from anyone who went back on it and it failed again -- and Dana Farber does it.
If Piqray doesn't work, if I were you and could afford it, I would self-fund. Will your oncologist support that? Can you get it if your oncologist doesn't? Lawsuit fear.
Ideally, you could get into a clinical trial. The one that Lna21 is in allows you to have been on CDK4/6 inhibitors that failed, no limit on how many. I am waiting for a new oral SERD trial. The pharmaceutical that made the one I was on discontinued the trial, unfortunately, because they had a med for another kind of cancer (prostate?) that they decided to pursue instead. Don't even have results from the trial I was on. The approved oral SERD in the US is only good for ESR1 mutation.
The NHS system here is dependent upon funding and the funding will not be made available unless every t is crossed and every i is dotted regarding data. We do not pay directly for our healthcare, so anything over and above would need to be self-funded if it is an expensive drug like this. I would go down that route if I felt like I was running out of options. After all, the money will not be much use to me if I'm dead! Also, I want to stay alive long enough to benefit from any new drugs coming onto the market.
The drug would be available from the same doctor working in the private sector rather than the NHS. I imagine it is a similar situation in your country depending on how much your insurance covers. I don't work and have no other insurance cover.
There are no clinical trials which I am eligible for at the moment, but that may change as time goes on.
I will ask about the ERS1 mutation when I'm in clinic on Monday.
I was diagnosed with breast cancer in 2003 with angiolymphatic invasion meaning it had left breast and was in blood. I had a partial mastectomy to left breast, 5 rounds of chemo and 6 weeks of radiation that was part of a trial holding breath to move vital organs out of field of radiation. I was not able to take Tamoxifen or Femara but all was good and I was considered cancer free. Until 2019 when a non stop cough producing blood, horrible side pain and high high blood pressure resulted in an ambulance ride to hospital. CTs revealed hundreds of nodules in both lungs, broken ribs and supraclavicular lymph nodes biopsy showing original breast cancer had returned. I started on Verzenio in May, and it worked immediately. However my quality of life was not so good due to the diarrhea and after 3 months....I went on 125 mg. Of Ibrance and Anastrozole. I was doing 3 weeks on and 1 week off and everything was showing no progression but the fatigue was overwhelming on week 3 and 4 so 2 years ago, I decided to stop the Ibrance and Anastrozole with hopes I'd feel better....actually I struggled with my breathing and my CTs showed lung progression. I asked to resume Ibrance at 100 mg. and Anastrozole as I explained to oncologist....it hadn't stopped working and he agreed. All CTs since have showed no progression and my oncologist has said I am in remission. Approximately a year ago, I decided to try the 100 mg. of Ibrance, Monday thru Friday and off on Saturday and Sunday due to the fatigue of week 3 and 4. I continued Anastrozole daily. Waited to see what tumor markers and CTs showed and then told oncologist what I was doing with schedule. At first he was pretty skeptical and said there is no research supporting this approach however my tumor markers, blood work and recent CTs have made him a believer and this week I was lowered to 75 mg. and continued Anastrozole. I am hopeful to keep it at bay for another 16 years. Just celebrated 4 additional years of life for a total of 20! I'm not saying this will work for everyone but I am saying, be your own advocate and be willing to try what may help you on your journey! I wish you all the best of health and longevity. I'm so sorry for the long read... I rarely comment unless I feel you can benefit from my experience.
Thanks Patti. What is instructive is that you stopped because of QoL. The fatigue is figuratively killing me, and I am tempted to stop Verzenio and/or anastrozole just to feel better. You did that and had progression. Hmm.
You were able to resume Ibrance because it hadn't failed. That is not my story.
I'm sorry EGCG from Green Tea. I was not aware that Turmeric would cause liver damage. Fortunately I have not had any indication from my monthly CMP that liver enzymes have been affected. I take 500mg 2x/day. Most of the info I get is from PubMed articles (NIH). My Onc is a traditionist. Sometimes I think he follows a flow sheet in stead of looking to treat cancer from a traditional and metabolic treatment.
hi everyone. I just re read this thread from 6 months ago. And wondered where some of you ended up vis a vis revisiting the cdk 4/6 drugs.
Elascatrant is not the miracle I hoped for so I am looking at a treatment change. It’s not a total fail, but I had a mixed scan. I am negotiating with my long suffering doctor to not do enhertu so am looking for any ideas…
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