Abemaciclib Verzenio for Stage IV
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chemo- they showed that in the lab, breast cancer cells exposed to CDK4,6 inhibitors can become resistant by mutating FGFR signaling, and so for those who have FGFR amplifications, they should take an FGFR inhibitor along with the Ibrance, or else they will not benefit ...
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I have an FGFR1 amplification (as well as 4 or so FGF amplifications that are linked to the FGFR3 and FGFR4 receptors) and lasted 15 months on Aromasin/Faslodex/Ibrance. Ibrance worked for me but likely would have worked a lot longer if I didn't have the FGFR amplification along with a host of other amplifications/mutations that confer hormone therapy resistance and impact CDK 4/6 efficacy.
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jfl: that’s kinda why I posted it. Perhaps these inhibitors could be available via compassionate use, to reactivate that combo for those tapped out on therapies? I’m also wondering if mebendazole or one of that family of drugs may be synergistic with CDK 4/6 inhibition.
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Luce, thanks for posting. It is interesting in how all of these targeted therapies are coming together. Compassionate use would be amazing. I am on an FGFR inhibitor in a trial right now as a single therapy and believe these drugs have a lot of potential if they can get the right one, that has tolerable side effects. I suspect FGFR inhibitors are much more effective in combo. I didn't qualify for the one trial I found that is testing an FGFR inhibitor with Ibrance and Faslodex. My hope is that these trials will find the right cocktail of drugs that can keep BC at bay for durable periods, like we have seen with HIV.
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JFL
You probably already answered this question couple of time, but I just ask it any ways, how did you learn about FGFR1 amplification? Is it through Henomic test? Wich one is more accurate?
Thanks!
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Ailuro, I learned about it through a Foundation One genetic panel test. Caris has a similar test and other companies have jumped into the testing arena as well.
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JFL
Thank you so much for replying . Do you think I should do the test, or wait and see if my meds are working? Onco said as long as meds give you benefits, there is no need to do genomic test and if there is any new growth on liver or any other area, then we will do a new biopsy and do the test. What do you think? I can trust what my BC friends tell me, better than any doctor
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Get it done now, as it takes forever to process and come back. It is doubtful that your pathology will change in the next few years, though it has been known to happen.
It is good to have the information should you need a new treatment plan, and horrible to have to wait 6 weeks for it when devising a needed treatment plan.
Jennifer
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Jennifer
That makes sence! I will bring it up in my next visit with my MO. Thanks again
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though remember that every time you have progression, the cancer has mutated and a new sequencing/biopsy will need to be done to decide on the next treatment, at which point the sequence analysis of your primary tumor will be moot...
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Cure-ious,
Every time you progress, you should get a new biopsy and genomic profile? I progress too fast for that scenario. I don't think my insurance would pay out for the tumor profile, like Foundation One. I'm still on the hook for $3K from my recent (and only) Foundation One report.
Or did you mean just a standard pathologist's look at the tissue, confirming (or not) whether you are still ER/PR/HER2 whatever?
Bone biopsies are unreliable, as you can't get a big enough sample without compromising the bone, and a liver biopsy is no walk in the park, even though mine is easy to get at. I can only think of skin mets as being easy to biopsy.
I haven't heard of anyone's major somatic mutations changing (other than becoming or dropping HER2, and becoming endocrine resistant, even though pathology will still show you as ER/PR+), but the technology has only been widely available for 5 years now, I think. This is fascinating. You and Bestbird are so informed about this stuff! So, I could have an ESR mutation, and that could change?
Has your MO been biopsying/genomic reporting like this? Has anyone else's? I've been at this for 7 years now, and no one at my MO's has said a word about this, which causes me to feel pretty frosty.
Mind spinning. I'd google it, but am a little too nervous about my upcoming visit to MSKCC for that trial, so I'm a little hysterical about everything right about now.
Wow.
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My oncologist's recommendations on testing are in line with Cure_ious's: you don’t do testing until/unless you need to to decide on a new therapy or a trial, because the info becomes somewhat outdated.
But I guess he alsotries therapies for response, which is probably common practice here in the US?
There could be existent info that is becoming useful from your old Foundation 1. Sometimes worth a second look, with new therapies emerging.
I don't have easy-to-biopsy tumors, so new biopsy last resort, unless liquid, which is of limited use.
You shouldn't be on the hook for $3,000 with F1. They promise to forgive patients whatever portion their insurance doesn't cover, up to full amount, last I checked. My insurance did not pay, and neither did I.Have you or your provider's admin staff contacted them about that?
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Haven't had anything done except the staining for hormone receptors, there's no point looking for PI3K, ESR1, etc in the primary tumor, they won't be there. Unlikely to have PDL1 expression, tho CDK4,6 inhibitor might elevate it, so it would be helpful if they'd hurry with liquid biopsies.
Luce, how are YOU doing?!! Are you still on Abemaciclib?!
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I had foundation 1 when I recurred two years ago. Biopsy during pleurodesis. I had a PI3k mutation then. Not much else jumped out at the time but my oncologist sometimes checks the results when we talk about new drugs.
I went up in dose, hoping it’ll stall resistance and keep more cells senescent. Awaiting TMs.
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Wonderful!! I'm glad you could move up the dose- for the PI3K, are you adding an NSAID? I'm getting excited for ASCO, abstracts should go online in a month...
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i've been on a mini aspirin for several months. does that count?
my onc is not expecting great things for us to come out of asco, or for any gamechangers to be on the horizon. i hope he is wrong.
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but to not just be debbiedowner here: there’s a woman in the cdk4/6 inhibitor Fb group who lasted for five years on Verzenio plus Arimidex.
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thinking about your PI3K mutant status, do they think you would have been resistant to AIs from the start? Obviously Abemaciclib was the right direction!
I'm so disappointed to hear not to expect much from ASCO, since AACR had so little (they made a big deal, deservedly, that CAR-T works on solid tumors, however we did already knew that from Judy Perkins--- and where were the PACE/JPCE trials and everybody else? lotsa trials have been going on for quite awhile now)- because your MO is connected to the clinical trial worlds, he would know when a big story is brewing. Any suggestions for secondline? Continue with the CDK4,6 inhibitor unless there is genetic evidence of resistance?
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Ailurophile -Regardless of when you have a Foundation One or similar test, the info will likely be useful! There are benefits to having it now and benefits to waiting for progression. I tend to fall into the wait until you need it for a treatment decision. Jennifer made a good point that there is no feasible way to have one after each treatment. However, patients may have a test done after a few treatments, after a few years or specifically to qualify for a trial. In my experience, the two key benefits of waiting are that:
- Some (probably most) trials requiring a specific alteration require a recent biopsy (within 6 months) and/or require a biopsy of the site that progressed. I have had two genomic panels done. For the first, my MO used my original lymph node tumor sample from 2014 1.5 years later in 2016. The second time, I required the test to be redone to qualify for an FGFR trial in 2018. Despite my first report coming back positive for said alteration, the trial required a specimen at site of progression no more than 6 months old.
- The technology is changing so rapidly that additional alterations are added by Foundation One throughout each year. The most recent report will mean you have the most full-some information that may show actionable alterations. For example, my first Foundation One report was done a few months before PDL-1, microsatellite instability and mismatch repair alterations were added to the test. (These are tests that can qualify us for Keytruda or Opdivo.). There were also numerous other gene alterations added between my first report in 2016 and second in 2019.
In a related but separate note, liquid biopsies may not be a good idea when you are on a treatment that is working. I had a large number of amplifications and a few mutations show up on both Foundation One reports done at times of progression. I had a liquid biopsy done while treatment was working and it came back with zero abnormalities. Since liquid biopsy is looking for circulating tumor cells in the blood, it may be that less or no cells with cancer mutations are circulating when treatment is working.
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excellent points, JFL! Good luck on erdafitinib!! are you the first one here to try this drug?!
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Thank you JFL!
Excellent and through explanation . I am so glad to be able to see different point of views and learn a lot here
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I was on the trial with Erdafitinib, Ibrance,and faslodex for two weeks. I dropped out of the trial due to the side effects of ERDA. I could not eat, had no appetite, had mouth sores, lips were sore, had no sense of taste, tongue was sore, soles of feet and palms of hands also were sore. It was intolerable. I have been off the drug 11 days now and I am not completely back to normal. I hope the drug will work for some but it certainly was poison for me. I lost 8 lbs during the two weeks.
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Wow, Meadows, that sounds traumatic and so disappointing! FGFR amplification is not an uncommon way that cancers become resistant to CDK4,6 inhibitors, and we need a good treatment. Hopefully JFL does not have it as bad, and/or they develop some kind of effective workaround for this drug.
What will you try next? The immunotherapy trial kattysmith is on (Opodivo plus EP4 inhibitor) is at least tolerable in terms of side effects.
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The approach at Oregon Health Sciences is pushing personalized medicine forward:
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cure_ious: I cant get that to display or play. But when I asked my oncologist how I could get into this program, he told me he’s in it and so I am too. I think that’s why I’ve been able to push for repurposed drugs and such.
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Wow I'm sorry to hear about that Meadows. Those side effects sound a lot like my initial side effects with Afinitor until slight dose reduction. After that almost everything disappeared. I suppose though that that may not be possible with clinical trials. So many of us here have needed to play around with doses to reach an optimal dose that allows us a much better QOL. I wich that were taken into consideration somehow in the trials also.
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Cure-ious, that sounds like a program we should all be in. It does seem like a combination of drugs at adjusted doses based on our tumor profile seems like the most logical way to fight this rather than blindly throwing treatments at it. I wish we could all be on it
It is surprising to me that MD Anderson is not on board with this. They have an entire building that is just for personalized medicine for Cancer patients.0 -
I don’t think they could offer a dose reduction as part of the trial. The trial is very new. I don’t think I would have agreed to a dose reduction anyway.
I see my regular oncologist next week. I was not doing the trial through my regular cancer center.
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On erdafitinib, I had a few tough side effects at the standard dose and had to take a week off due to too high phosphorous and ALT caused by the medication. I resumed at a lower dose and all of the other major side effects subsided except for painful mouth sores.
However, it is all for naught. I had a PET scan and erdafinitib is not working. I will be meeting with MO to start something else tomorrow. Likely Navelbine. Hopefully, erdafitinib will work better for some of the others on the trial meadows participated in, which combined erdafitinib (now newly FDA approved and called Balversa) with Ibrance and Faslodex. I thought about pursuing compassionate use to take it with Ibrance and Faslodex given that I do not qualify for meadows' trial but can't afford any more treatment delays right now. I have lost so much treatment time waiting for the trial's red tape to clear. I spend more time in washout periods than I did on the actual drug. I only took it for 7 weeks and was on a drug holiday for more than 1 of those weeks. Basically, I took the drug for less than 6 weeks. To add further insult to injury, not only are my liver mets increasing and more active, which are the usual suspects for me, 1 bone met lit up as well. I had very late stage, grave bone mets throughout my entire skeletal system, coupled with uncontrollable hypercalcemia, when diagnosed and by some miracle became NEAD in bone mets w/in 3 months and stayed that way for over 4 years. The bone damage took about a year to heal. Anyway, feeling a bit stunned and scared right now.
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jfl: thanks for letting us know what’s going on. Here’s my 2c: I would ask my doctor to apply for compassionate use of erdafitinib anyway, because you may want to try it again in that triple combo down the line. Not super likely that the company will supply it for free, but worth trying. If it’s available off label for bc,they might’ve provide it through their patient assistance program.
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