Are you currently (or have you been) in a Clinical Trial?
Comments
-
Nicole, EZH2 is a protein/enzyme, like CDK4, and there is a good inhibitor for it; in trials for some cancers but did not see breast- these papers come out and it can take forever for them to end up in a trial. But at least we know about it, so if we see it listed in a trial, like maybe one open to any solid tumor, it may work well.
You do VERY WELL with your understanding (whereas I've worked in this area 40 years..)
When new cancer drivers are identified, like AAMDC and TRIM37, its not surprising that genetic tests would not be looking at those yet- however, all they have to do is make a PCR probe, so those genes could be included in next versions of these tests relatively quickly
0 -
Thanks Cureious! I understand now.
0 -
Cureious, thanks for the explanations on the subtype clusters. You have a gift for explaining things. I remember seeing a post on that awhile back but had no clue which subtype I was. I know I don't have the PI3KCA mutation so I'm guessing I fall into cluster 1. I used to beat myself up, wondering what I did to cause my cancer to start growing again. Now it makes sense, it really is th e type that drives recurrence.
0 -
Cur ious I have several questions which I hope you'd be kind enough to answer. I've had cancer close to 4 yrs. Been on several hormonal Tx's which worked 3 mos and stopped. Taxal chemo did work but after 6 mos my ONC said enough because of the neuraphty (sp)in my leg. (I had skin cancer on my breast size of half dollar and he chose chemo to stop possible ulceration).
In this past July he put me on A/A, first three month scan some shrinkage and no SE. Then the cancer on my breast started traveling to whole breast, under it, above it, and across my chest in like 3 weeks. It went so far and then it stopped. The second three mos of A/A it seemed like a different drug, won't bore you with all the side effects I went through.
He has me on Havelan trying to knock back cancer on my chest, I've been on it 2 months and the cancer is getting crusty which might be a sign of dying.
He told me before Havalen that that was the last treatment he had for me because I couldn't handle any of the stronger chemos.
About three months ago, I ask for Found 1 testing and he said no because it hasn't had a chance to mutate yet.
Yet three weeks ago he sent in a sample OF THE ORIGINAL biopsy and said it came back with a 100% cell mutation. He said an older medicine piqary should work.
Am I missing something?
0 -
Snooky, Sorry you have been through the gamut, not fair! But given your history it makes sense the cancer is probably driven more by PI3K/mTOR and to try that type of inhibitor- and it sounds like he is saying that you have a PI3K mutation, which would explain why the endocrine therapy did not work well for long. PI3K mutations do not tend to change during treatment . Piqray works well but you want to get the good advice on antihistamines to avoid a bad rash, and will want to try a keto diet or just do water-only fasting for 12-14 h overnight in order to let your blood sugars go low as possible, because the drug elevates blood sugar. You could also look for a clinical trial where you can combine the Piqray with a SERD or the ARV-471.
Other drugs are being developed for PI3K mutations, one is SDX-7320, which inhibits metAP2 that drives many of these cancers. Trials showed that SDX-7320 attenuated the high blood sugar problems caused by the PI3K inhibitor alpelisib (Piqray), and importantly, the combo improved the anti-cancer activity, indicating that SDX-7320 could provide real benefit to breast cancer patients taking a PI3K inhibitor. The company says they intend to open enrollment for an upcoming clinical trial in metastatic ER+/Her2- breast cancer patients with a mutation in the PIK3CA gene in first half of 2021, so that trial is well worth looking for.
Also, altho he said no other chemos, Enhertu or Trodelvy are targeted chemos that work way better and are better tolerated in terms of side effects, so I'd keep those on the list for sure. Second opinions can be very helpful and also to help guide you through the clinical trial world
0 -
Cur ious I thank you so much for all of your sharing of your knowledge. God Bless You. I was just so concerned that he used an old tissue sample. Fasting, yes I can do that easily
Have a blessed day
sue
0 -
They continue trying to improve chemo. A trial added Aurora A kinase inhibitor Alisertib to taxanes for MBC, it clearly helped somewhat- PFS was 10.7 months compared to 7.1 months, and 44% of the group with Alisertib made it one year, compared to only 15% taking Paclitaxel alone, and with Alisertib they were able to use less of the chemo. Next will be to try combinations with oral taxane
https://www.medwirenews.com/oncology/breast-cancer...
0 -
UCSF has been engineering CAR-T cells to recognize two proteins, rather than one, on a cancer cell surface, and thus better hone in on the target and not hit normal cells, and and think they have a good one for HER2 MBC and for glioblastoma- they say these are ready for clinical trials:
The publication in Science March 2021
https://science.sciencemag.org/content/371/6534/11...
https://www.ucsf.edu/news/2021/04/420441/smart-cel...
https://www.scienceboard.net/index.aspx?sec=ser&su...
0 -
Very interesting cureious, thanks for sharing.
0 -
Illimae, Sure thing, I added another discussion of the UCSF work to the above post, it looks really good. But your post also reminded me that I had wanted to look a bit more at what other trials might be out there for CAR-T for Her2-positive cancers.
Here is one that will open in June 2021. They are recruiting now, but only at one site (Baylor College of Medicine, TX). It is phase one, and they will inject an accessible tumor with an oncolytic virus, to get some cell killing and rile up the immune system. Then they follow that with CAR-T against Her-2. The CAR-Ts from UCSF have been engineered so that they will not "exhaust", and some other CAR-Ts have also put in a fix for that problem, but I don't know if these Baylor CAR-Ts have such a fix. If not, I think they can just inject more of them at later times; still this is one of several things to consider when evaluating different CAR-T trials. The UCSF one is also presumably better targeted just to the cancer.
https://clinicaltrials.gov/ct2/show/NCT03740256
Below link is an interesting report of a CAR-T response to HER-2 in a child with rhabdomyosarcoma (solid tumor). Another trial run by someone at Baylor. Because that CAR-T cell had no fix for "exhaustion" they first treated with chemotherapy, to deplete lymphocytes in general, which apparently gives more favorable environment and space for the CAR-T cells to expand and keep growing and not get "exhausted" or depleted. In this case, the child responds, but then the cancer comes back six months later. At that time they then re-administered the CAR-T cells, and only a single cycle of chemo-CAR-T was given. At the time of the report, the child was 19 months off T cell treatment and still cancer-free. In this case the cancer was 75% HER2+ but they saw that even non-Her2 cancer cells got eliminated, so they attribute that to the effective cell killing opening up the tumor to better attack from the immune system overall.
https://www.genengnews.com/news/her2-car-t-therapy...
0 -
However, highlighting this is early stage work, a group showed that Her-2 cancer cells can resist killing by CAR-T cells, by switching off a cell death pathway that depends on gamma interferon. so the have to work on that too
https://www.eurekalert.org/pub_releases/2021-02/vd...
0 -
The PACT CAR-T trial at UCSF has never been recommended to me. Perhaps because it's not technically a BC trial? I asked about it once a while ago after Theresa told me she had talked to David Oh. The response from my MO was tepid at best. She never seems to be a fan of general solid tumor trials. The trial specifies HR+ for BC inclusion.
Hugs, Susan
0 -
Hi. I stayed on the AZC9833 trial (oral SERD) for one more month. That will officially end now. I have shocking results from my lung biopsy. I have liver mets that are estrogen positive, and for the past 3 years my liver has remained tumor free. For the first time, my lung nodules were large enough to biopsy last week. Over the past 3 years they have slowly grown with my largest nodule going from 4mm to 17mm. The smaller nodules from 2-3mm to 10mm. A few days ago, I received my results from my liquid blood biopsy, and I had the Pi3k mutation. Today I received my lung biopsy results and I am triple negative!!! OMG, I've only researched estrogen positive over the years. I am at a complete loss.
0 -
KarPC...wow that is a lot to take in. I too am ER+ PR- HER2-...they say that when we are PR- we have more chance of going to Triple Negative...I pray you get a lot of information on TNBC pages. Its crazy that your liver tumors are ER+ and yet you have triple negative ones too elsewhwere... As soon as you know your treatment plan please let us know. (((((hugs)))))
0 -
KarPC- I was just reading about the "converters", and one thing that is clear, although the converted cancer cells lack ER, PR, and HER2 expression, they are molecularly quite different from cancer that is triple-negative from the start. Analysis of these cells show they have multiple different signaling pathways on, and differences in protein expression, etc, compared to TNBC, so its really like apples to oranges. Which makes sense when you consider that they have only examined the expression of 3 genes out of some 30,000 total. One thing is clear- this new cancer subtype is much more sensitive to immunotherapy, far more sensitive than TNBC even. They don't know why but are studying that for sure. So consider trying some promising combo immunotherapy at some point. And can it return at some point to be ER-positive again? will be interested to see if your MO keeps you on some endocrine therapy for that reason...
0 -
Cureious...I found your reply to KarPC to be so encouraging...and even....encouraging for me if that eventually happens to me.... thank you for that post. I actually want to show that to my Oncologist....
0 -
KarPC
What a shock. Hopefully you will get some clear direction and treatment that will knock back the cancer. So glad forthe tests to help in the decision process for learning what could be driving the cancer.
Dee
0 -
Thank you so much Dee & Nicole for understanding my shock.
Cure-ious - we are so lucky to have you here sharing your knowledge! I agree with Nicole that your comment was encouraging.
I am getting SBRT to my largest lung nodule (mapping on Monday). My onc called and we had a very short conversation. She did say that I could still have estrogen receptors in my other lung nodules, so that is something to consider for my next treatment plan. We are waiting on another test (PD-L1) to see if I qualify for immunotherapy. My appointment with her is on Thursday. I will give you all an update after my appointment.
0 -
Hugs to Everyone here, and sorry to break in here, but we are looking for people who identify as black and who are currently on or have been part of a clinical trial to share your experience for possible inclusion in a special podcast episode.
Please PM the Mods or email mjenkins@breastcancer.org if you are interested in sharing.
With appreciation, The Mods
0 -
KarPC,
Sorry to hear about the progression in your lungs. I have also been experiencing slow progression to my lungs and pleura. I assume when they did the biopsy they confirmed that it was TNBC. One of the women in my support group was told she had TNBC in her lungs and ER+/HER2- everywhere else. After a number of failed treatments, they figured out that the tumors in her lungs were lung cancer, not TNBC. Sounds like horrible news but she has done well since finding this out since they could treat it appropriately and she has had success with lung cancer treatments along with her HR+ BC treatments.
Some good news for TNBC and HR+ people, there is a relatively new Phase I trial for a new ADC developed by Daiichi Sankyo, developers of Enhertu.
ORR (Objective Response Rate) of 43% and DCR (Disease Control Rate) of 95%!
Hugs, Susan
0 -
Thanks Susan. Yes, it was TNBC. Gosh, what a story - another good reason to get a biopsy with a new site.
0 -
Susan
That trial you listed appears To includeEr/pr+ her2-
https://clinicaltrials.gov/ct2/show/NCT03401385
But it does say must be resistant to endocrine therapy.
Dee
0 -
Dee...thank for posting that...I think that may be me...
0 -
Dee,
Thanks for the correction. I meant to type "HR+", not "HER+". I corrected my text.
Hugs, Susan
0 -
Susan, Wow, target enrollment of 770 for a phase one trial, they clearly expect this is going somewhere. A Trop2-targeting ADC, well, the more the merrier...
0 -
An update for the trial Androgen Receptor agonist/booster, Enobosarm, was presented at the ESMO breast cancer conference:
Enobosarm treatment in evaluable patients with measurable metastatic AR+ER+ breast cancer who had progressed following treatment with an estrogen blocking agent and CDK 4/6 inhibitor (Ibrance) resulted in a clinical benefit rate at 24 weeks of 50% and a best objective tumor response of 30% including 2 complete responses and 1 partial response (meaning tumor shrinkage). The overall mean radiographic progression free survival for the 9mg dose was 10 months. The 9mg dose of enobosarm was selected for the Phase 3 ARTEST study that is anticipated to commence in June 2021.
These numbers look good- most on the trial had already progressed on at least three prior therapies, including chemo and Ibrance, yet half made it at least six months with stable disease.
0 -
Cure-ious,
Thanks for sharing the good news. I had confirmation today with my Cirus report that I'm AR+. Any discussion about SEs?
Hugs, Susan
0 -
Susan, This is the drug that some bodybuilders take as a supplement, because it builds muscle and bone, so the side effects are ones we want! The company is excited and thinks they can go up against I-F in firstline and for adjuvant therapy, because they think the SEs are more tolerable than the other estrogen inhibitors. The issues for us are 1) is the cancer still endocrine-sensitive/ER-dependent? because Enobosarm works by boosting AR to inhibit ER; 2) the trial was testing it as monotherapy, maybe it be better in combination with CDK4,6 inhibitor or something else? (but then again another drug could mess with the SEs?); 3) the trial they did had relatively small numbers, because they only realized that this drug should work well when a paper was published in Nat Comm last fall
The latest from the company (posted below) indicates they are considering two trials, one that will be Enobosarm alone as a third line of treatment after failure of I-F, and another one that is in combination with Versenio, but they say that one is second line of treatment, so its possible that both trials will exclude prior chemos. One would think they will also put a trial up for later stages because there are a lot of people who have not had a chance to try the drug. But anyway, getting access to the drug, that's the job of our MOs, right? and this one is even sold as a supplement, tho I read the FDA considers it a drug and illegal to sell OTC
0 -
Enobosarm a Novel Oral Selective Androgen Receptor Targeted Agonist, for the Treatment of Androgen Receptor Positive (AR+), Estrogen Receptor Positive (ER+) and Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer – Phase 3 ARTEST Clinical Study and Phase 2 Enobosarm Combination Study.
We expect to commence our pivotal enobosarm Phase 3 ARTEST clinical study in the second quarter of calendar year 2021. Enobosarm is the first new class of targeting endocrine therapy in advanced breast cancer in decades. Enobosarm is an oral, new chemical entity, selective androgen receptor agonist that targets and activates the androgen receptor (AR), a tumor suppressor, in AR+ER+HER2- metastatic breast cancer without the unwanted masculinizing side effects. Enobosarm has extensive nonclinical and clinical experience having been evaluated in 25 separate clinical studies in approximately 1,450 treated subjects, including three Phase 2 clinical studies in advanced breast cancer involving more than 250 patients. In the two Phase 2 clinical studies conducted in women with AR+ER+HER2- metastatic breast cancer, enobosarm demonstrated significant antitumor efficacy in heavily pretreated cohorts that failed estrogen receptor targeting agents, chemotherapy, and/or CDK 4/6 inhibitors and was well tolerated with a favorable safety profile. In the fourth quarter of calendar 2020, the FDA agreed to the Phase 3 multicenter, international, open label, and randomized (1:1) ARTEST registration clinical trial design to evaluate the efficacy and safety of enobosarm monotherapy versus physician's choice of either exemestane or a SERM as an active comparator for the treatment of metastatic AR+ER+HER2- breast cancer in approximately 210 patients who have failed a nonsteroidal aromatase inhibitor, fulvestrant and a CDK4/6 inhibitor (3rd line treatment in a metastatic setting) The primary endpoint is median radiographic progression-free survival.
In a separate clinical development program, enobosarm in combination with abemaciclib, CDK4/6 inhibitor, will be evaluated in a 2nd line metastatic setting in AR+ER+ metastatic breast cancer. A Phase 2 study to evaluate the efficacy and safety of enobosarm in combination with CDK 4/6 inhibitor (abemaciclib) compared to estrogen receptor blocking agent (Active Control ) for the treatment of AR+ER+HER2- metastatic breast cancer in patients that have failed an estrogen receptor blocking agent plus a CDK 4/6 inhibitor (palbociclib) is expected to commence in calendar Q3 2021.
0 -
Even if the enobosarm doesn't have a positive impact on the cancer, the prospect of a neutral agent that improves quality of life is exciting. My only worry is if it has a negative impact on some. Do clinical trials just rate overall positive response? Do they in any way screen for if say 25% of the participants do worse than expected? What if half do better, and half do worse on a treatment? How is that screened for and interpreted? Median survival might be the same, but some live longer than expected? Not that I am suggesting this is the outcome, but curious how they screen for that.
0
