Are you currently (or have you been) in a Clinical Trial?
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Theresa45- I also have the Y537S ESR1 mutation-- it just showed up in last month's G360 test, despite my not being on an AI (nor SERD) for almost a year...it was not present in my G360 test last summer. Really surprised it showed up after 8 months on Xeloda. Must have been brewing at undetectable lives prior to the switch in meds in August. It confers resistance to AIs and indicates a poor response to fulvestrant-- but my onc/researcher suggested an oral SERD trial (different med than you are looking at) or an immunotherapy trial.
I have opted for the immunotherapy (IO) trial and pending the last hurdles (labs and ECG, already have 'RECIST-measurable' disease for the first time and my most recent mets have been biopsied) I will start June 13--nivolumab (PD-1) plus ipilibumab (CTLA-4) and bicalutamide (anti-androgen) but am very interested in the potential for these oral SERDS to potentially overcome ESR1 mutations, especially the 537 mutations. There is some pretty good pre-clinical evidence suggesting efficacy in these cases.
Please keep us update if you enroll...I'm excited AND nervous about the IO trial-- the increased IO-induced autoimmune complications that occur with combination therapy are real and potentially deadly, but am very well informed about the side effects to look for and have been well and strongly counseled to call AS SOON as any of a myriad of symptoms appear, especially cardiac or neurological...I'll let you all know how it goes.
Hope you all are well, and finding a moment of joy in your days.
Elizabeth
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EV11 - Thanks so much for your thoughts! Xeloda was relatively easy for me too, so I'm really disheartened to be moving on from a treatment that can last for a long time. Progression is NO FUN!
If I go on the G1 Therapeutics oral SERD trial, I will absolulely share my experience. It is strange that your ESR1 mutation appeared after a break from AIs. Mine appeared after 18 months on letrozole on G360. The oral SERD trial is a phase 1 dosing trial, so one of my concerns is that I would be given a relatively low dose compared to the dose used in mice/dogs. The trial started at 200mg and I would receive 800mg. The trial will continue increasing the starting does for new patients up to 2000mg, but my dose would not be increased. There is a Phase 3 trial of another oral SERD (Elacestrant), but it is randomized with 2/3s receiving the oral SERD and 1/3 receiving standard of care hormone therapy (fulvestrant, anastrozole, letrozole, or exemestane). My sense is that, for me, the oral SERD has an easy side effect profile, but are not very likely to work. My fear is that the met that just appeared in my liver could explode without a stronger treatment. That's why I'll also be trying to line up local liver treatment.
I've read a little about the IO trial with nivolumab (PD-1) plus ipilibumab (CTLA-4) and bicalutamide (anti-androgen). It sounds very promising. Do you have the PD-1, PDL-1 or CTLA-4 markers? Do you have macrosatellite instability or high tumor mutational burden? Are any of these required for the IO trial? My oncologist is suggesting a pembro + ATR trial (from BAYER) for me, but it will not be open at Stanford until August or Sept 2019. If it was open now, my oncologist would favor it over the oral SERD trial. The immunotherapy trials seem to offer more hope for a durable response, but have a higher risk for side effects at least compared to an oral SERD.
Thanks again for sharing your ideas. I hope that you will have an exceptional and durable response on the IO trial!!!
Theresa
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Wow, EV11 and Theresa, Such interesting options!
I see the makers of the Lasofoxifene SERD got the FDA to fast-track it based the fact that it destroys ESR1 so well, so they were able to use the "lack of a good alternative treatment" clause to their advantage. Interesting that both oncologists are excited about SERD and immunotherapy trials, we know they have been gaga about SERDs for a long time, they are much stronger than Faslodex, but the immunotherapy interest is new, and hopefully comes from hearing good results with ER-positive patients- Good luck!! Everybody appreciates all the information we get from your postings!!!
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Thanks for the support, Cure-ious.
I have a PIK3CA mutation, so I am also considering the newly approved Alpelisib/Fulvestrant or Alpelisib/letrozole combos, although I already progressed on Ibrance/Faslodex and letrozole alone.... and I have a pesky ESR1 mutation. I also have not yet been on A/A. It would be nice if Alpelisib plus an oral SERD was an option! Stanford did not run any alpelisib trials, so I would be their first patient on Alpelisib and they said it could take some time to get alpelisib.
My new liver met is making this decision a lot scarier for me. I don't want my liver to explode with cancer while on an oral SERD monotherapy.
Best wishes to all! Theresa
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Theresa and Elizabeth, I also have the ESR1 Y537S mutation. Disheartening that it is less common and less likely to respond to certain treatments. I have had my eye on some of the SERDs and SERMs in the works as they seem to be able to treat certain types of resistance that other hormone therapies cannot do. I do have some hope that eventually drug cocktails, combining various hormone therapies with more than one targeted therapy, will reverse hormone therapy resistance in some people. I would like to do Piqray/alpelisib at some point but feel more comfortable doing it with an additional targeted therapy to try to cover various different bases. Afinitor/Aromasin didn't work for me but it did demonstrate a flicker of hope. Although it did not stop progression, it did slow down the metabolic activity of the cancer so there was something going on. With a third drug added, perhaps it would work. I am currently on Navelbine and tamoxifen which seems to be working. My liver enzymes and alkaline phosphatase have returned to normal levels since starting the combo 6 weeks ago after being elevated for the last year or so, ever since I had Y90. I am so happy as I was off effective treatment for a long time after my recent clinical trial failure with the FGFR1 inhibitor, erdafitinib.
Theresa, I look forward to hearing about what you chose to do and will follow if you take the SERD option.
Elizabeth, I will be following your IO trial as well. What is the significance of the anti-androgen? Were you required to test positive for androgen receptors? Best of luck!
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woke up with a strange headache at 4.00am again...this time I didn't take the ibuprofen, I drank instead a glass of homemade ginger tea and massaged the aching area: the top of my head.
I must work on my mood...since I started taking this drug I've become more than depressed....kind of lifeless and hopeless...I've developed a sort of zombie lack of mental and physical capacities... I can't find enough strength and interest to tackle even the smallest task...
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I'm sorry to hear that, Frisky. It's hard to keep one's head above water when we don't feel well, to put it mildly. Would a visit to your wonderful acupuncturist help? Let your care team know how you are feeling and call on your support system. I keep my cards close to my vest, so taking off my mask andreaching out is really hard for me...I hope you are smarter than I am in that area. Keep in touch.
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Frisky, I'm sorry that this trial drug has such difficult side effects. Nausea, headache, lack of sleep and not feeling well are strong mood deflators... not to mention constipation. I hope that your oncologist can improve your side effects. Your ability to maintain your sense of humor even when feeling ill has been inspiring, but it's impossible to always be up with this disease. I really appreciate your honesty. Please be gentle with yourself and talk to your oncologist. I'll pray that super-Ibrance is destroying your cancer cells making it all worth it.
JFL, Thanks for your input! The ESR1 Y537S mutation is one of the two most common ESR1 mutations (the other is D538G), so at least it is being studied. I hope that Navelbine and tamoxifen will work well for you for a long time!!! If tamoxifen (SERM) is effective for you, then maybe the Lasofoxifene SERM that got the FDA to fast-track will be a great option for you.
Best to all!!
Theresa
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Kattysmith, Theresa...I can't ask for additional help from my medical team. All they do is prescribe more medications, that come with SE, to control the SE of the initial medication.
It's a negative loop, that my mind refuses to accept as good for me. All I have been doing, since I started this protocol, is to manage the se, I no longer have a life, and my mind feels fried already.
I have to find the strength to get back to more of my complimentary protocol in between the two daily sessions. I have been focusing on the needs of my body, now I have to support my brain before I lose whatever is left of my capacity for rational thinking.
No matter how much I want to feel good about this drug, everything about how it makes me feel, tells me they don't know what they're doing, they have failed us for so long, nothing is gonna change anytime soon because the mentality is the same.
They are so full of themselves while prescribing these dangerous and useless medications ....maybe my brain is shutting down so I can comply....
I’m gonna start taking SAM-E, hopefully I’ll start snapping out of it!
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Frisky--- My prayers are for you today. My friend, what can I do? I understand that more meds, more SE, is not the answer. Can you tell your medical team that the trial is messing with your thinking and emotions? Can they lower the dose given to you? QOL must be addressed. This would not work for the general public if it effects them as it is doing with you.
I wish I could come visit with you, hold your hand, and help you through these feelings. Giving you a BIG HUG from here.
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Candy thank you for your prayers and caring...I have already brought up a possible reduction. They are not interested....plenty of patients on this trial are on a reduced schedule, and many have been allowed a reduction after they took the maximum, but in my case, since I just started they need to see what this amount will do...
This leads me to believe that the results so far haven't been that good...
Today, after drinking additional cups of tea, that normally would make me wired, I was still struggling to keep my eyes open, i'm constantly dozing off for hours at the time. When I attempt to get something done...I'm just too physically tired and mentally unfocused to see it through ...which leads to more dozing...
I'm experiencing a type of depression that's really disconcerting....I could, of course, cheat and take less pills, but I'm trying desperately to give my team the benefit of the doubt, and honestly support their efforts.
I couldn’t easily live with myself if I had to outright lie.
Tomorrow I'm going in for bloodwork....maybe if I saw actual results, I would feel better about the sacrifices I'm making...let's all pray there's a payoff in all of this for everyone
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Frisky--- I will be waiting to hear from you and your results.
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Frisky, It is helpful to have tumor markers as an early indication of how you are responding to the drug. Given all these side effects, I wonder why they did not try this pill first as just a CDK2 inhibitor, since that can have its own unique SEs apart from Ibrance. Are there any facebook pages or twitter feed from other people who have tried this drug? The depression is particularly concerning, I remember reading about this as a possible side effect for some MBC drug, can't remember now which one it was. Wishing you a deep restful sleep tonight with no headaches and no nausea, just happy wonderful dreams.
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Yes..wonderful dreams Frisky. One brave girl and proud of you.
I monitor this site and take copious notes.
Thank you everyone.
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Cure-ious, would the Lasofoxifene potentially replace Faslodex and Zometa or just the Faslodex? Can't wait to see my med onc after ASCO - she goes every year....sometimes I feel like Dorothy, hoping the Wizard has something to help me (us)——LOL
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Hello, all... first, I want to say how nice it is to have you "out there"...I so appreciate everyone sharing your experiences, thoughts, tips for dealing with side effects, and treatment considerations. It always gives me much to ponder.
Cure-ious, JFL and Theresa- there is no requirement for this IO trial for the ER+ MBC patients to have androgen receptors-- the bicalutamide is used more for it's effects in the thymus gland (stimulatory to T cells, apparently) than it's anti androgen actions, although in ER+ patients that might be beneficial as well. For the TN patients, AR positivity is required--not sure why the difference. I'll have to ask my oncologist that. Also, they are looking at the presence of PD-1/PD-L1/CTLA4 and other immune markers, but at this early stage there is no requirements at any level for inclusion in that regard. There is a pre-enrollment biopsy, and a cycle 2 day 1 (42 days per cycle) on-trial biopsy to see if/how immune characteristics may change after the three doses of nivo (every 14 days) and 1 dose of ipi (every 42 days.) That may inform future arms.I will be only the 4th patient on it (between my cancer center and MSK --soon to open enrollment there, but they are not quite ready-- they are hoping to enroll around 140 patients in all.
Theresa-Can you do local therapy to your liver lesion and still have another untreated source to serve as your "measurable disease" lesion? Or would you consider starting the SERD trial and if you don't have rapid stabilization /reduction in the liver lesion move on to local therapy? I am in occasional contact with a researcher who studies ER resistance (primarily in lobular disease) and he is very optimistic about some of these oral SERDs for treating ESR1 mutant disease (less so about the SERMS for lobular.) There are moments I am worried that I selected the wrong trial, but am hoping that if I have bad side effects on the IO that I will get off the trial before there is serious or lasting side effects and will try again to get onto the SERD trial-- there are still a few spaces left. And if not, there is also a venetoclax trial in Spokane (also requires travel-ugh- but I would do travel to it for sure. After the first 6 weeks or so it drops to monthly visits. There is a good bit of early evidence that for lobular (frequently BCL-2 amplified) it is very effective, and I just saw a very positive initial report from a trial about its efficacy in mostly ductal patients.) Also, I'd consider sitting tight for a few months to see if an Aplelisib plus SERD trial comes into being-- it is a very logical combo and could help address some of the ESR1/PI3K mutations that are starting to be seen after CDK4/6i exposure.
I keep telling myself that there are a lot of promising treatments on the horizon. I am a widow, with a 15 year old daughter. I desperately want to live AT LEAST long enough to see her through her first year of college (3 more years....) and would truly love to see her through her undergraduate path and into her early independent adult life. She is a bright, kind, resourceful young woman and I think that she will have a positive impact on her community, if not on a larger scale. I'd love to see how she will 'turn out."
Frisky-- yikes!!! Your experience sounds dreadful and I am so sorry that trial developers/PIs don't seem to understand that trying to find maximum tolerated dose really is not the best path to take...miserable side effects can drive many off what might be an otherwise tolerable and effective treatment at a lower dose. I hope that your body adapts soon and that this becomes easier for you. I echo Cure-ious' suggestion to find a FB or other group (here??) to find other patients and compare experiences and responses.
To everyone else-- I hope that you find a path to comfort, and even more so to an effective and tolerable treatment.
Peace, Elizabeth
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https://images.app.goo.gl/szKPCChTuKsmRCNN7
They say a picture is worth a thousand words...
the medication makes me feel mentally, physically and emotionally exhausted....I told the trial nurse today...she was, however, too young to get the cultural reference when I mentioned Jack Nicholson and the final scene inone flew over the cooko's nest.
her response followed by a big smile: would you like to see a psychiatrist?
I'm afraid that's not going to help. I said.I am usually a very optimistic person. Only last week, when I was off all treatments, I was convinced I would make it, I would be cured...now when I'm not dozing off, I want to write a will....there's a definite link between cause and effect.....this is a SE of the medication...
Nope....she couldn't see it...she suggested I start taking the Ritalin, which I will do tomorrow morning, so if i start posting incessantly, you'll know where that's coming from
so here's a little clue about clinical trials for those of you that are considering joining one...
Oh....I forgot the best part....these SE are BEFORE they add the Letrozole....that will require a zombie reference...the classic George Romero's the night of the living dead, comes to mind
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Frisky...GGGGGGAAAAAHHHHHHHHH! Jesus, Mary, Joseph, and Chucky.
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You poor thing......I know what you are describing. Those are just some of the effects of depression. I've been in and out of them all my life. I truly feel for you.
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I just woke up and out of my medication induced stupor....and Kattysmith you have me howling from laughing so hard...chunky? Don't give me any ideas!....
I have now three hours of mental and emotional clarity to enjoy before my next dose... and then like Dracula I will pull the cape over my head andgo into hibernation.
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I have been lurking here, learning tons. Thank you, everyone who contributes.
Frisky, please be aware of where the line is for you, the line between unselfishly contributing to this trial along with hoping the drug will help you, and putting yourself at too much risk and being too miserable. Look out for yourself. If I remember correctly you had other options but wanted a trial because the other (standard) treatments offered seemed too hard on the body?
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Cure-ious, regarding a trial mbc drug that caused mood disorders, were you perhaps remembering the pan-PIK3 inhibitor buparlisib from a couple years ago? Quotes copied from a BCO page:
"Buparlisib improved progression-free survival by a couple of months, but the problem is it was quite toxic," said Ruth O'Regan, M.D., professor of hematology and oncology at the University of Wisconsin and one of the study authors. "The most serious side effect is it gets into the brain and causes anxiety and depression. It also causes elevation of liver function enzymes, which is another concern."
Even though women with a history of mood disorders were not allowed to participate in the study, the effects of buparlisib were so severe that a few patients attempted suicide while taking buparlisib.
"So even though the study shows us that there is a signal there and that by inhibiting this pathway, it does appear to be beneficial for patients to some degree, the toxicity's a problem with this drug," Dr. O'Regan added.
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Shetland...I hear you and will definitely protect myself, thank you for the reminder to be careful. I try to during these windows of clarity in between sessions.
My plans is to see if the SE improve as my body gets used to the drug...if I find them persistently unacceptable I will take other measures...they expect me to be on this trial for two months, but I believe that when something works, it shouldn't be too hard to find out. Plus, they started this trial months before I joined, I think they know already what to expect, and it's not very good, otherwise why not be more open about the results?
The problem is, I truly don't want to undergo chemotherapy—which I equate as similar in pain and suffering —and there's nothing else, other than clinical trials with the same fundamental limitations in scope for me.
I'm starting to find the status quo absolutely disgraceful, medications that cause more suffering than the disease, are simply unacceptable!!
Shame on our doctors! after so many decades we still don't have a cure, or a permanent management of this disease.
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Shetland, Yep, yep, yep- that is exactly what I read! It was buparlisib- they had people in clnical trials who were actually attempting suicide! And these were not people who were at all prone to depression before taking the drug. These drugs affects cells in all parts and systems of our bodies, and there is no way studying a dish of cells in the lab is going to predict the effects on brain neurotransmitter functions, etc. Very important to pay attention to all of your symptoms, Frisky, and never mind if they don't get the Cuckoo and Nurse Rachett references, at least you haven't lost your sense of humor!
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Disturbing detail about buparlisib and several people trying to commit suicide on it. Wow.
Frisky, I have been on numerous treatments, mostly chemos (7 lines, plus a few short-term, interim/bridge treatments on top of that, plus Y90). None have been anywhere close to what you are describing as far as side effects are concerned. I am worried about the toxicity of this drug. I just dealt with major toxicity in my failed erdafitinib trial where I put myself in some danger for a while there. Take care and I hope your condition on the trial drug turns around and that it is super successful. If not, there are other options that WILL give you a much better quality of life. If quality of life is your reason for avoiding chemo, and this is how this drug makes you feel, I am reminded of a funny saying that a person is "saving the sleeves off one's vest". Praying for a quick turnaround for you on this second gen Ibrance.
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I, too, was an anti-IV chemo poster child and swore I would never have it. This was in 2003 when I had borderline Stage 2 BC and all I was interested in were alternative / complimentary avenues in addition to the rads and Tamoxifen. Cut to 12 years later when subcutaneous tumors were popping up like crabgrass on my arms, shoulders, and neck. My MO at MDA presented my case to the group there and gave me a couple of options that they had discussed. A slow approach with oral meds or start on IV AC, the infamous Red Devil. The fact was that my high-grade tumors were very aggressive...you wouldn't believe how fast they were growing. It was obscene and fucking terrifying. I immediately decided on the chemo and within two weeks, my tumors were melting away and continued to do so for the two months I was on it. Before each infusion, they front-loaded me with pre-meds, fluids, steroids, and something that made me feel groovy (I forget what), so I was pretty much in la-la-land. Yes, I lost my hair, had some constipation at first, and a few days of mouth sores. All in all, I tolerated it really well. After two months, we talked about whether I wanted to have another course of AC or if I wanted to try Ibrance / Letrozole. Ibrance had only been on the market for a year then, but I decided to try it. I had two good years on that protocol with no major SEs.
When I got liver mets in the spring of last year, I had a brief course of IV chemo combo (Carbo & something other than Gezmar) that SHOULD have knocked it back, but didn't. I felt fine except that my RBC plummeted, so I had to have the Neulasta patch and later on a transfusion (which made me feel fantastic, I totally get Dracula now).
So Frisky, take care of yourself, only you know what is tolerable for you, both physically and mentally. I'm certainly not posting the above to try to talk you into chemo, it's just my experience. Someday I'll tell everyone about my funny first day of chemo.
Onward through the fog,
Katty
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JFL and Kattysmith thank you for caring and sharing your positive experiences...I think about the many women like you on these boards often, because you've always been so reassuring about undergoing chemotherapy, and are indeed a role model for me.
I will need to first get over my deep phobia and distrust that's building up against the wisdom of a genetic approach to cancer treatment. But, I'm no longer sure on how to resolve that problem either, because last night, the metabolic approach, which I believed to be the alternative for me, since it appeared easier and natural, turned out, upon a closer inspection, to be as treacherous.
Last night, I listened to this YouTube video, where Thomas Siegfried, a researcher from Boston University, explained his metabolic approach to cancer. Basically, he believes that is necessary to starve the cancer cells by blocking their uptake of sugar and glutamine.
His explanation seems logical, until you realize that the solution he offers is a ketogenic diet in combination with a glutamine suppressor. The problem, as I see it, is that these are severe dietary restrictions, if they are to be carried out for months and years.
Plus, he never explained how this was going to work, since glutamine is found in greater amounts in the food groups that constitute a ketogenic diet....And where in this country, can a person find clean sources of those foods?
Have you noticed, how those tv shows that feature wholesome ketogenic recipes, take place on location, on beautiful farms with grazing, happy animals in the background?
Meanwhile....since this morning I woke up very late, feeling still the soporific effects of the drug, with tummy aches, and no appetite whatsoever. I decided to skip my morning dose till I have full control of my body and senses.
I think I will need to revisit Joe Tippens and Jane McLelland success stories to lift my spirit. Will also try to go shopping and get some fresh air and exercise.
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Update. Being off the medication is helping me get back to my old self.
I did take the Ritalin to see if it would help me gather enough strength to go outside. It did, but it's so mild, I have not noticed any particular or weird SE. No heart fluctuations as warned by the nurse
As I walked back from TJ where I bought groceries and a bunch of beautiful peonies—my favorite flowers— I had a moment of lucidity, and realized why the medication is hitting me so hard....and why it might not affect others the same way.
Apart from the obvious suppression of physical, mental and emotional activities, it seems to totally destroy my creativity, intuition, and a profound belief I have in myself. It renders me extremely vulnerable as it removes self knowledge.
The medication, in the amount prescribed, is deadening those abilities so radically, I couldn't even remember what was making me feel so strange and out of sorts, other than using the correct reference to the Jack Nicholson character. In this amount, the med is capable of changing one's personality—at least in people like me.
So there you have it....I had to write it down, in case I forget it when I resume taking the medication.
I believe, I have also found the solution to my predicament...vis a vis Pfizer and my doctors....since they won't agree to lower the dose, I will simply not take it when I'm not feeling well....I will let them arrive at their own conclusions....
In this way: a-I won't need to lie, and b-I'll be accurately reporting the SE, important information that they will need to take into consideration..
One more thing...I'm convinced my cancer cells are feeding primarily on sugar and carbs...although, Jane McLelland says that breast cancers feed primerely on fatty acids.
Recently, I have been diligent in reducing my sugar treats to only frozen blueberries.... today, however, as soon as I got back home, after putting away the groceries..although I had had breakfast already, I couldn't resist eating two ciabatta rolls with Irish butter and raspberry jams....
I believe my cancer cells had been so deprived, they hijacked my will power and shopping choices at TJ's...only my theory of course...fact is that now I feel amazing!
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I'm thrilled that you are having a good day, Frisky!
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May God bless you Frisky. You do what you need to do. To keep you you. Yes the trial is important, but YOU are more important. And you eat a sweet treat once in a while. You deserve it !!!!
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