Ibrance (Palbociclib)
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jaycee, very interesting article and a different approach than I’ve heard about before. Sort of like a “zen” approach, not attacking but suspending.
Yes, it does make a person weary dealing with the disease. I got away by myself yesterday, drove an hour on some winding country roads full of springtime color to get to a mall to do some retail therapy, and it actually did get my mind to a different place.
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Nova- Ha!! What do YOU think about it?!!
It reminds me of that story came out the other day about the oncology group testing the idea continuous cycling through of different chemos, starting a new one before the other one has failed. Don't give the cancer a chance to mutate and become chemoresistant. One could make the same argument about I-F, prevent the cancer from becoming endocrine resistant, and same for immunoresistance.
The problem is we have all of these strong drugs- but what combo do we use them, and in what order? the number of possibilities is too large for clinical trials to sort out, at least in the near term, altho it provides plenty of fodder for researchers, they won't run out of questions anytime soon.
Just as a small example, there was a report in the literature, based on the experience of 25 patients, that going on to Affinitor-Aromasin after Ibrance-Femara does not work. they said the 25 women got an average of only 4 months before they had to move on (remember that means half got less, half got more). That is well below the 9 months PFS that was reported in the original Affinitor trial, which was done using patients that had not been on Ibrance. OTOH, the trial had many more people, so maybe Affinitor does work fine after Ibrance, and these 25 people they surveyed were just unlucky, the survey size being too small to be meaningful.
But still, should we be willing to try Affinitor?
Maybe we can crowdsource an answer from the people who read this blog- has AA been an effective treatment for anyone previously treated with Ibrance (with Faslodex or Femara)?
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Cure-ious, thats interesting since there seems to be more evidence that Ibrance does not really work after affinitor. My MO still tried Ibrance since its such a blockbuster drug and it worked for me for about 4-5 months after afinitor failed. Now that I think about it, Ill take those 4-5 months? But afinitor is a much tougher drug than Ibrance so I can see why one would be more apprehensive to try it.
Just from reading about everyone's experiences, it seems like whichever way one goes, with hormonal treatments the first drug seems to work longer than the second. Maybe the cancer has just mutated to something much smarter after it beats the first drug. I'm probably just rambling at this point, but just an observation..
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Jaycee, yes, I too am tired. I am nearing my 3 year cancerversary so I cannot imagine five years. And I have been on the same treatment the whole time! I was thinking earlier today how tired I am of being sick and limited... What I am saying is you are not alone and I understand. I don't have the energy to research alternatives when I am working so hard to keep this one working and keep my family happy at the same time. Maybe winter was just just too long this year!
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Thanks to all for airline/drug issue answers. Even before Mets I was paranoid about traveling with pills cause most of the time I just set them up in daily drug holder..And most airline suggest they be in the bottles from pharmacy..am I ok with individual pills in pill holder??
Jaycee 49..A time to rest.and trust your MO.I have so much confidence in mine and her continuing education..BC forums etc.I will leave it in her hands if progression occurs..I don't mean to sound..like a Pollyanna but any of us could die from car accident..stroke..whatever...Please just let go of the research for a bit..I bet you feel less tired..Just a caring thought...
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Thanks, everyone. I wish I was having a Poor Me Evening and was all better now. BUT this morning, I was again dealing with a bill from my hospital system from five years ago, a Medicare "take back" as it were. I'm making progress (I guess) even though I seem to have more records in my possession than Medicare does. In my mental state, I guess there is some relationship between this five year old bill and my five years in this mess. The thing is, I never got a break. My MBC was discovered during my year on Herceptin so it never ended, even falsely.
Lakewoman, I trust my MO but I trust myself more. And one small piece of information for you and flying. I developed lymphedema because of a flight to my son's wedding a year after my original treatment. (Surgery, chemo, radiation) I learned afterward that all kinds of precautions should have been taken during that flight like extra compression, etc. I was never warned that flying could cause/worsen lymphedema, even though I talked about my trip to my son's wedding ad nausem at all doctors' appointments. (So why should I trust my MO?) During lymphedema treatment with my physical therapist, she told me if I ever flew again, I should go back to the arm thing that can be adjusted (and tightened) for the time of and around the flight. I packed my meds in checked luggage but kept a few days supply in carry on for a lost luggage situation. I can't help it. I was a Girl Scout. Be prepared. And have plans B, C, and D.
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Lakewoman, I never have any problem with keeping my pills in a pill holder for flying, and I usually keep that in my purse for check in. I think I would take the bottles for international flights though.
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Thanks so much intothelight..big help.will never think of it again..unless international..
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Jaycee, sounds very much like you have just had enough right now. Completely understandable and no-one will REALLY know how you are feeling. .... Pissed off, disappointed, exhausted and frustrated might ring bells though.You rightly counselled me to try and speak with someone from work - I did that with someone I trust and felt much the better for putting the thing in perspective.
Do you have someone to properly talk with... who will not judge, or tell you they know how you feel ( I usually have to stifle the impulse to punch the person who says that) or tell you to pull yourself together and how lucky you are really to be alive...( the person who said that to me will never speak to me again after my response... and do I care... naw!).....but someone whowill properly just listen? I’m not talking about a professional (although that’s an option I suppose).
I’ve weirdly found those ears in unexpected places... occasionally very good friends and often a person who doesn’t know me well at all but just gets it. I try hard not to overload any one person.... if it’s too much for me it’s probably too much for them too. But I know I need to offload and be good to myself.
Also a wee break maybe? From all of us... the appointments, the reading and just all of the STUFF! ( except taking your meds... that’s a given). Do something very self - indulgent maybe? Aaaand you’ve thought of all this already I’m sure!
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You're right, Karen. I actually feel better today because of an appointment I had this morning with my gyn. Her nurse listened to me (really listened) for about 15 minutes and then the doctor did the same for about 20 minutes. I was mostly talking about issues with them (like why did it take 48 hours for them to call me about positive culture results) but I got around to my total fatigue with the whole system. They were wonderful. Not rushing me at all. Very unusual. You might not understand this being there with NHS, but hospitals here are buying most medical practices and running them like the rest of the corporation. Not how medical practices should be run.
I also have a therapist who I will call soon to see. I take wee breaks from BCO from time to time. No break from appointments, though. Pet scan next week. But I did find ears in an unexpected place. I'll be looking for more of those.
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ann273- Re your comment about each subsequent therapy not working as long- I listened to a podcast where breast specialist Ingrid Mayer at Vanderbilt said that she thought the total progression free survival was the same between someone who took AI alone then at progression- fulvestrant plus CDK and then at progression got Everolimus with someone who got AI plus CDK and at progression went to fulvestrant and Everolimus. If you get a long PFS on AI alone you may get less on the CDK than someone who goes straight to CDK.
My MO told me that there was a 40% chance that Everolimus or Xeloda would work at all for me. The PFS is about 4 months on Xeloda and per the small study 4 months on Everolimus- it seems to me that it takes 3-4 months to find out if one of these drugs is even working unless you have very predictive TMs and they change during treatment. So you are adding together the people who it doesn’t work in with the people it does and hence some of these very low PFS times.
I don’t know if Afinitor is working or not for me- I am on month 2 and TMs did go down after month 1. By the way - it costs $14,258 ( plus $117 for the mouth wash and $99 for generic Aromasin.) per month.
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Nkb, you're worth it.
Jaycee, I think we all just want to be heard, don't we? I'm glad today was better.
Love from PatGMc
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Good, that's a relief Jaycee.. one wee step at a time I think. Thankfully you've got some Ears! I keep telling my lot they need to be clean Ears... no wax... there's a picture you really don't want in your head....
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Nkb- that was a question I had too- if the PFS is only 4 months and they scan every three months, then how do you even know if it worked at all?! But, in your case, you do have TMs that you can follow, so no worry, its working!!
I'm leery of trying AA, but wouldn't want to skip a good treatment for no good reason
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Nkb, yes I have definitely observed that if someone was on an AI and then moved on to either CDK4/6 or Afinitor they worked for lesser time. I went straight to afinitor, so who knows if it was just the Aromasin that kept me cancer free and afinitor added a few more months. I suppose we'll never know now. I hope your side effects on Afinitor are'nt too bad and you are being able to manage them well. I'm excited that your tumor markers are dropping! Lets see what the scans show in a couple of months!
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Hi all- I was reading up on FGFR amplification, especially those involving FGFR1, which is a common way that ER-positive MBCs mutate to escape from Ibrance.
The report below indicates that IF the cancer had both an FGFR amplification and an mTORC1/Pi3K mutation (like PI3KCA or PTEN) then it was are MORE LIKELY to respond well to PI3K inhibitors.
Although the patient sample size was small, I also thought it was interesting that none of the patients had responded to the FGFR inhibitor drugs, not sure how great those drugs are.. one paper says they work better if combined with a VEGFR inhibitor (in cultured cells; in patients the side effects might be awful)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC49652...
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Hi Cure-ious, I think other P13ka drugs work well, but didnt we see quite a bit of literature that said that FGFR mutated cancer is resistant to Alpelisib even if they have a P13ka mutation also?
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Nkb, that PFS of 4 months on xeloda / capecitabine, was that based on use as a second line treatment? It seems awfully short. There are a number of women on here that have used xeloda for years in the metastatic setting. My wife progressed on tamoxifen to metastasis in her liver, went on xeloda and it worked like gangbusters. She was on it for over a year when she voluntarily switched to letrazole and ibrance. There are women on here who have benefited from xeloda for 2 or more years, one I believe is still on it around the 5 year mark.
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I find all this talk of progression and pfs, and the different treatments a bit mind-boggling. One would think there would be a national database set up where all our mbc patient stats were entered everytime we progressed for how long till progression using which drug etc. Hard to believe it would take that much time to make entries. I think it would be a goldmine.
I too wonder about what is in line for me next. Dr doesnt want to discuss it as it could be a while and there could be some mutation or something new to use. Too many possibilities to waste breath. After being on ibrance one year and now off for one year he only said he could put me back on ibrance when my tumor markers went up.
The nurse and PA said to discuss with dr the order of drugs to use and Pat said all AI,s are the same therapy so i dont understand how just changing the target therapy qualifies as a change or would make much difference. And maybe it doesn't thus only 4 months on average tilll progression.
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A question I didnt get an answer to is, can I go back to an AI if I haven't had progression on it? Its just fadlodex for me now. And soon xgeva quarterly. PA hinted that was out of "order" that you use the drugs and to talk to dr. Right now I'm going with "I dont need to know ". I've been saying that lots lately.
GAILMARY
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hisband11- I read the 4 month PFS for Xeloda on the Xeloda thread. It surprised me- I have never used that drug. It seems like we see people that these drugs work great in and others that it doesn’t work at all and that gives us a lower PFS for the people it DOES work in.
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There also seems to be some comments that Ibrance is only effective up to four years.
But the drug was only FDA approved in 2017.
Some women were in the phase three trial which began in 2015 and are still on it.
One article dated from 2017 said over 50,000 women were prescribed Ibrance. In other words, in two years time, 2015 to 2017, 50,000 women were prescribed Ibrance.
Who know how many more since that time.
I don't think we know yet how far out Ibrance can be effectivewith that many women taking the drug. I appreciate this thread, yet there is a lot we women do not know. And there is only a very small fraction of women with mbc who use this forum. At one time several years ago, I took a poll to find out what our numbers were, out of curiosity and about 350 women members with mbc responded.
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Ann273- Good memory! The above paper did not specify which PI3K/mTOR inhibitor drugs they were talking about, and that study came out in 2014, before alpelisib was available.
Regarding Alpelisib, the trial found that patients with FGFR amplification alone did not respond at all, whereas cancers containing both FGFR amplification and a PI3KCA mutation did show a benefit, however it wasn't as strong as cancers lacking an FGFR amplification. Similarly, the everolimus trials reported reduced response in FGFR amplified cancers, and they did not address what happens with cancers containing double FGFR-PI3K mutations.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC50859...
The FGFR inhibitors supposedly work best on highly amplified FGFR2 genes (mostly seen in TNBC). My question is what works best for the FGFR1 amplified cancers that are more commonly seen for ER-positive MBCs, especially the ones that have become endocrine-insensitive? I wonder if these are sensitive to other drugs in the pipeline, like BET inhibitors, HDAC inhibitors, CDK7 inhibitors, etc, because Alpelisib and everolimus are not options. And, do those cancers respond to immunotherapy?...
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OK- FGFR-amplified cancers are definitely not sensitive to immunotherapy, due to high levels of MAPK signaling. there are trials to combine MEK inhibitors with immunotherapy for these cancers, but right now its just for TNBC patients.
Here is a current suggestion for FGFR1 amplified ER-positive cancers:
https://www.ncbi.nlm.nih.gov/pubmed/30914635
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Hi ladies! I was diagnosed in Feb 2015 at the age of 38 w/mets to my spine (T5 and L2). I've been taking tamoxifen and lupron for over four years. Unfortunately, this week, I progressed in recent scans w/new mets in my spine (S1) and liver. My MD is suggesting CDK 4/6 (Palbo/Ibrance). My question for all of you: Should I complement w/aromatase inhibitor (Letrozole/Femara) or SERD (Fulvestrant/Fasoldex). The standard seems to be the former, but recent PALOMA 3 study indicates better PFS w/the latter. Thoughts?
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Cure-ious thank you for all of your posts and research. I was talking with my Oncologist about getting a second opinion before progression on Ibrance/Letrozole.
I’m not looking to travel far at this point so I’ll with do Georgetown or Hopkins.
I do have FGFR1 and PIK3CA so I’m going to see about the trio suggested.
I’ve read mixed findings on tumor burden load, mine is low.
It’s hard to know which mutations are drivers and which ones are passengers.
Biomarker Findings:
Microsatellite status - MS-Stable
Tumor Mutational Burden - TMB-Low (0 Muts/Mb)
Genomic Findings:
AKT3 amplification
PIK3CA H1047R
FGFR1 amplification
MDM2 amplification
MYC amplification
CDH1 splice site 2296-1G>A MYCL1 amplification
NSD3 (WHSC1L1) amplification RAD21 amplification
ZNF703 amplification
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It looks like a combination of an FGFR inhibitor with CDK4/6 is recommended for FGFR amplified cancers and there is a trial at Vanderbilt that is currently doing just that. I do remember someone on bco who was ont he trial but dropped out due to terrible side effects. I am curious to see how that trial pans out. It seems like FGFR is one of the pathways the cancer takes to resist CDK4/6 so it sounds important enough to figure out how to manage these cancers.
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Cure-ious, if possible can you point me to any literature on FGFR1 cancers not responding to immunotherapy?
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Nova, it will be very interesting to see what gets recommended. I also wonder if the CDK7 or CDK12 inhibitors work on these cancers; because it is a common way cancers escape Ibrance, we need more discussion on good options for cancers with these amplifications. I remember Z had FGFR1 amplification and was trying to find options
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One conclusion is that the FGFR1 amplification is not a strong driver of cancer cell growth (and therefore not very responsive to FGFR inhibitors), whereas cancers with high levels of FGFR2 amplification are very sensitive: "In vitro and sequencing studies suggest that FGFR is not a dominant oncogene in FGFR1-amplified cancers, whereas FGFR2-amplified cells are highly addicted to FGFR signaling and demonstrate an apoptotic response to FGFR inhibition."
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