Are you currently (or have you been) in a Clinical Trial?
Comments
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Shetland and Ann, I had a similar but not exact mutation show up ending in G rather than B: PIK3C2G. I don't know anything about it and haven't been able to find much information out there. I hope that some of these additional PIK3 mutations will have be targeted in therapies in the future. I also have a PIK3CA.
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Shetland- you have the PIK3C2B too? Yes ILC with mets to liver and bone for me. I haven’t had time to do much research on it but just lately happened to be looking through clinical trials and stumbled on a trial that I think required it. I’ll try to find it. I could not handle the SE of tamoxifen way back when so I would hope for the Gemzar to be the magic bullet for us! I see you got to NEAD with Taxol. I just started it and hoping for the best.
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With kattysmith as the sole beneficiary of immunotherapy we can point to around here, I thought this was an interesting report about how hard it is for oncs to get approval from insurance to try immunotherapy off-label, when its not a straightforward FDA-approved approach, supported by phase 3 clinical trials and all. And how incredibly expensive it is in such a situation. Nobody is close to a big phase 2 or 3 trial using immunotherapy for ER-positive MBC, so we need more brave souls to step up and take a chance on some of the earlier stage trials.
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Went to see a dermatologist who specializes in cancer patients, Dr. Bernice Kwong, at Stanford. Apparently, MSK has a dermato oncology program as well. She said that my itchiness and rash is likely an immuno response to having been on Alpelisib. There is data about this kind of post-treatment response with Hodgkins Lymphoma patients. Alpelisib was used for Hodgkins Lymphoma before they tried it on MBC. I had thought that I lucked out because I didn't have any serious side effects while on the drug. Now, I'm paying the piper. She took two skin biopsies and may know more next week. So far, almost three weeks of crazy itching and rash on my neck, arms, knees, sides of my hips, back. I think that they need to know more about these drugs before they are approved.
Hugs, Susan
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Cure-ious, you are right on the money about that. There is so much talk about Opodivo and Keytruda. I think the problem with Er+ MBC is there are multiple options that seem to have been tried and tested and made it through trials and when people run out of them, the tumor load may be high for immunotherapy. Even if we reduce the load by trying chemo for a few months, it may make us ineligible for the trial.Its really such a conundrum
I'm scared that MBC will be one of the last ones to get on the boat.0 -
SusaninSF, now that I come to think of it I had very itchy skin on afinitor especially in summer months. I'm sure your dermatologist will suggest something solid for you. I started using neutrogena's body oil or jose maran's argan moisturizer (this works amazingly well but was prohibitively expensive) and both helped me quite a bit. Eventually the itching subsided (maybe after using it for so long, my body just adjusted to that side effect). Hope you find a solution soon!
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Susan, thanks for the information about rash with Alpelisib!! Recorded & remembered! That is why GC had to drop out of the trial, remember!!
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Ann199 and Shetland- the PI3KC2B mutation upregulates Cyclin B1: CDK1 activity, and I think this can be targeted by the CDK7 inhibitor - there's one trial with an injectable CDK7 drug now, but other oral inhibitors are coming
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC49512...
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Shetland and JFL - The trial I thought was for the PIK3C2B was NCT03218826 which is for the PIK3CB so unsure if they are the same or not or would be able to target our mutations. Maybe it targets the “pathway”?
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Thank you, Ladies, for the thoughts and info on PIK3C2B. I will watch for CDK7 news and trials.
Some quotes from the article Cure-ious linked: “Taken together these data indicate that PI3K-C2β is barely detectable in non-neoplastic breast tissues, whereas it is clearly expressed in breast primary tumors where it correlates with proliferative activity. Furthermore data indicate that PI3K-C2β is highly expressed in lymph-node breast cancer metastases“ and “Importantly, Kaplan-Meier curves for invasive breast cancer cases indicated reduced survival in patients with PIK3C2B alteration“. (Why can’t we get better genomic tests at early stage?! I would have been more aggressive with what the docs thought was a low-risk bc.) Near the end of the article ‘These data support the conclusion that PI3K-C2β has a key role in breast cancer progression and metastasis. Nevertheless, to the best of our knowledge our study is the first to actually report an increased protein expression of PI3K-C2β in breast cancer cell lines, primary breast tumors and corresponding lymph-node metastases.“
I remember looking at a trial with a broad (I think it’s called pan-class) drug that was not specific to PIK3C2B, but more generally attacked that pathway, and my onc telling me that the pan-class ones so far had turned out to be too toxic. And I think that trial was stopped. (Sorry, I moved recently and my notes are still in a box somewhere.)
Ann, I think the 2 may be important, as the article talked about class 2 PIK3, of which PIK3C2B is one, not having been studied much. But I’m in way over my head. Why not.
I’m sorry if this vears off the thread topic too much. But trials ought more and more to address the unique profile of a particular cancer, right?
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Shetland- I also heard that the pan PIK3 drugs were too toxic as well. The UCSF doc said that the study that was being done on CDK 7 was actually a combo of CDK 1,2,5 and 7 and was being studied for TNBC- also quite toxic with fatigue, severe rash and diarrhea. she called it something like adynaciclib .. I don't know if they are separating out the different CDKs in other studies.
I'm excited about a reformulated Ibrance that Miaomix might be starting.
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Nkb- Dynacyclib is the drug that hits all those CDKs, and its an older drug with a lot of off-target kinases, so I hope the more selective CDKs are better. I saw a new trial with CDK7 oral treatment today (link below), however it is early days, just phase 1, and they are testing as monotherapy since it hasn't been in humans. CDK12 inhibitors should be great too (based on the effects on cultured cells in lab), and some that might be CDK2-specific are being developed. everyone is hoping they don't have bad side effects
https://clinicaltrials.gov/ct2/show/NCT03770494
https://www.imperial.ac.uk/news/185666/new-class-drugs-could-help-tackle/
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my MO is proposing Morpheus trial. Anyone on this trial? Any comments.
I have recurrent TNBC and am now waiting for a solid tumor that has two dimension on CT before I will be considered.
I am anxious to find out more but little to tell at this stage from MO due to confidentiality with Hoffman Roche who is managing trial in Australia.
Kind regard and best wishes to all- Helen
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Shetland - I sure agree - this is important stuff. Thanks for showing specifics.
“Furthermore data indicate that PI3K-C2β is highly expressed in lymph-node breast cancer metastases" and "Importantly, Kaplan-Meier curves for invasive breast cancer cases indicated reduced survival in patients with PIK3C2B alteration".
Sure wish they had known this five years ago too and had access to drugs that may have been beneficial.
I have only 14% PIK3C2B, 26% PIK3CA but 52.9% CDH1. Guess I'd have to check further with the trials to see if I would qualify. But it is so frustrating and exhausting to sit here in my PJs today trying to research. However, I hate standard of care and am trying to be my best advocate.
Cure-ious- that CDK7 trial sounds interesting! Thanks.
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the main point of the PI3K3C2B paper was to show that the cancer growth actually depends on this mutant kinase. ie, just because a mutation pops up it doesn't mean the cancer is using it to grow. also the suggestion is to wait for the cancer to be fully endocrine resistant (high percentage of PI3K mutant cells) before adding a PI3K inhibitor to the regimen, alto a different strategy is to add the inhibitor up front to delay recurrence and accumulation of the PI3K mutant cells
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blainejennifer - thinking about you. did you get through all the final steps for the car-t trial? hope everything is moving forward the way you hoped.
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Thriving Mama,
The last hoop is to see if my tumor tissue expresses enough mesothelin to enter the trial. MSK has a chunk of my liver monster, and I should hear the results next week.
I wish it could be faster.
Jennifer
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Blainejennifer - the waiting is so hard! wishing you peace of mind in the meantime.
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BlaineJenner-
More on the CAR-T trials for solid tumors: they expect to really be "moving the needle" on this therapy in the next five years; hoping that you get to be one of the pioneers!
https://www.onclive.com/publications/Oncology-live...
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Cure-ious,
Thank you for that article. Now, if we can just hang on until they have it figured out!
No word from MSK yet. Small groan of nervous despair.
Jennifer
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I'm bumping up this thread in case anyone wants to chime in on how they are doing?
BlaineJenn, what was the upshot on the CAR-T trial, were the mesothelin numbers too low? They will soon come along with a trial for MBC, surely!!
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I started cycle 6 of my trial last Tuesday, after being off of the study meds for a couple of weeks due to my mystery ailment that was almost certainly a blocked salivary gland. My next scan is coming up soon, so I should know by early June whether I'll continue down the garden path or get thrown into the wilderness again. Now that I'm over my painful yuck, I'm feeling well, but it hurts too much to cross my arthritic fingers and toes in anticipation of my next scan results.
Hope everyone is doing well!
Katty
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Katty, I'm so glad that your mystery ailment has resolved and that you are back on the trial medications. I love your analogy about walking down the garden path or being thrown into the wild! I hope that you will have a long, sunny walk along the garden path with no more mystery ailments!
Thanks for updating us! Theresa
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The results of the PARP Inhibitor clinical trial (TBB Trial) that I was on is reporting at ASCO 2019. The treatment was talazoparib (Talzenna) monotherapy and eligible patients had BRACA-like DNA repair mutations. I am the patient listed as gCHEK2/gFANCA/sPTEN which means genetic mutations in CHEK2 and FANCA along with a somatic PTEN mutation. I had a good response for 10 months with minimal side effects and a very normal quality of life. There was also an arm of the TBB trial for triple negative breast cancer patients that may still be recruiting. There is a similar trial for the PARP inhibitor Olaparib (Lynparza) which is larger, at multiple sites and currently enrolling patients. That trial also includes patients with somatic BRACA mutations.
The link for the TBB trial results is: http://abstracts.asco.org/239/AbstView_239_265331.html
Here's a description of the Olaparib trial: https://www.dana-farber.org/clinical-trials/breast---female/trial/17-428/
Both Talazoparib and Olaparib are FDA-approved for metastatic breast cancer patients with BRACA mutations.
Theresa
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theresa, I'm so happy to hear that PARP inhibitors do not come with a whole host of awful side effects! Although I do not have the BRCA mutation, the CDK12 inhibitors eliminate expression of BRCA and allow PARP inhibitors to work on cancers that do not carry BRCA mutations. So hopefully there will be a trial combo of PARP plus CDK12 inhibitor, which the rest of us could benefit from. And by then they will surely have added on immunotherapy, and we will (finally) be off to the races...
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Can you believe I still haven't heard from MSK? So, I finally got brave enough to call them. Turns out they haven't heard from their pathology department whether or not my liver mass has enough mesothelin. They are, understandably, peeved.
I believe that the universe is letting me have time to take care of my sick dog. She's had imaging, fine needle aspirations, and all they can tell me is that it's not Immune Mediated Thrombocytopenia. They'll get the cytology reports tomorrow. As it stands now, they are thinking that it is some sort of major infectious process.
And, beloved progeny is home from college, so we don't have to spin plates to get to MSK and take care of the critters at the same time! Oh, Universe, I love how you operate, but it would be nice to have an informational note attached.
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The universe is infinitely patient, however we are not, and the forces that be have taken pity on you and published something you might like to read whilst you are awaiting the verdict:
https://www.onclive.com/publications/Oncology-live...
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Immunotherapy Emerges as Valid Option for Breast Cancer
Improved understanding of immune evasion, discovery of selective immune checkpoint inhibitors
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Just heard from MSK. I do not produce enough Mesothelin in my tumor to be eligible for the trial.
Going to take a few hours off. Maybe get a new lipstick. Then trial hunting commences anew.
Jennifer
PS: Yes, I am completely bummed.
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I am so sorry to hear it Jennifer. We were all rooting for you and I can only imagine how bummed you must be about it. That being said thank you for going through it all to be a pioneer. The red tape, the emotional ups and downs and everything else you have gone through is admirable. For most of us in this position all we can do it try and keep at it. I hope your next trial or treatment is once that sticks and works for you. Hugs.
Ann
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