Are you currently (or have you been) in a Clinical Trial?
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Hi Phet- CDK7i looks great in the lab, but no data yet from clinical trials, and maybe a stretch for it to work on its own?
A new drug Eganelisib has been fast-tracked by FDA for use with immuno and chemo in TNBC:https://www.targetedonc.com/view/fda-grants-fast-t...It is being tested in the phase 2 MARIO-3 trial, scheduled to end next August:https://clinicaltrials.gov/ct2/show/NCT03961698
But no sites outside of US, plus they exclude prior chemo or targeted therapy, but something for your list if it moves to phase 3
The people who have responded best to chemo-immuno are those who converted from ER-positive to -negative, so are there any good options for chemo-combo trials?
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Thanks for your post Phet, that's very interesting and something to follow.
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Thank you Cure-ious and Buttonsmachine! Yes I am also worried about the lack of clinical trial data so far on the CDK7 and it being single-agent (though very attracted to the side effect profile of that!). I have a friend who is doing a PhD in the Imperial College lab that helped develop this one (under the trial I linked) so I might press her to let me know if there's anything coming from the trial so far. I know that in theory they're not meant to let on how trials are or aren't working but I guess that information must filter out somehow. The professor running the lab that developed it tweeted something last year about exciting results coming but i guess he would say that (and who knows what counts as 'exciting').
I definitely do want to do a chemo/immuno combo trial as well - at present it seems there are none that would quite work for me but then we don't know what there will be open in the UK when I need it. There is the Begonia trial which is pembro will various different chemos and targeted therapies but it needs to be first line treatment. There are some very experimental ones I would be tempted to try - one with Keytruda and an oncoloytic virus! - but I know chemo+immuno would be the safest option. I will cross all fingers a good option for that is on the table when I need the next treatment line.
I've also heard that people switching from ER+ to TNBC have good rates of success with chemo/immuno so I'm really hoping that's the case for me. I have an intermediate tumor burden according to foundation one (8), which doesn't seem exciting but as the average for tnbc mets is about 2.5 I'm hoping that also works in my favour. We can but cross our fingers with these things and pray to the breast cancer gods
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Hi Phet. Maybe you can get an idea of how the trial is going from her. My trial is at my regular treatment clinic, so I was able to ask my regular oncologist before I started the trial what she thought of the it, and if she had any patients doing well on it. She was able to answer that. One month after I started the trial, the clinical trial doc saw me, and was gushing with excitement because my trial got approval for phase 3. He shared this information with me before any announcement had been made. Anyway, not much but any bit of information helps us make a decision.
Dee - what a bummer to hear your scans were put off for a week.
I have good news! I am able to continue the AZD9833 (oral SERD) with everolimus trial. They decided my existing tumors were considered stable, and my tumor markers were good. Multiple people looked over the CT scan of my lungs and thought the new activity was from covid rather than cancer. I am relieved. ~Kar
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KarPC- that is fantastic news- 💃🏻💃🏻💃🏻 Happy Dance
Dee
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Excellent for both of you guys; Phet please let us know anything about CDK7i, this would be wonderful news for endocrine resistance if it works, there have been all kinds of rumors over the years that it didn't work or had bad SEs, so I've kinda forgotten about it
I got Foundation One back, nothing actionable, and more to the point no ESR1 or PI3KCA or HER2 mutations that would explain progression. they listed a couple "maybe something" mutations, CHEK2, DNMT3A and spliceosome SF3B1, which would seem unlike to cause endocrine resistance so far as I can tell. the CHEK2 mutant I157T is not as bad as a more common truncating one, which can be resistant to Faslodex..So I'm guessing my MO will move me to Ibrance-Faslodex next week..
Tumor mutation burden=1 (whomp, whomp) so the DNA repair machinery is still (mostly) working and something new is going to have to come up in immunotherapy to be a good option...
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Cureious ~ A low mutation burden is good! I went from Ibrance/Letrozole to Ibrance/Faslodex. Now that a few Oral Serd trials are looking promising, using your falsodex with Ibrance seems like a good idea. BTW, the Ibrance/Faslodex combination was far easier on me than the Ibrance/Letrozole. I learned that the Letrozole was to blame for so many of my negative side effects. There was a small study by Dana Farber (last year?) about taking a 3 week treatment holiday from Ibrance to possibly reverse resistance. I wonder if you could start faslodex as a mono therapy for a month then add back in the Ibrance? ~Kar
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cureious- was there a reason for choosing Ibrance/Faslodex combo over Verzenio/Faslodex? you are a good researcher so I figure you have a reason
Positives of Verzenio for me was everyday med, probably crosses brain barrier and less neutropenia. I did not have the D issues that some get. I also tolerated Faslodex much better than all the AI’s
DEE
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Curious and Dee you guys seem to be very knowledgeable. I was wondering if you could give me any advice on how to get started on my list of future medications and trials. I've been writing down all the trials that have been on this site and different meds that people have mentioned. Just wondering how to put it all together. Where to start? How you guys track and know each drug would work for you? Also how to read the foundation 1 report. And what I should be watching from there?
Any information would be helpful.
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Jjzn, for standard already approved treatments, have you got Bestbird's book? https://community.breastcancer.org/forum/8/topics/...
For new trial things that come up here, I usually bookmark the study or article & I write down on my own paper a keyword - usually the medicine being trialled. Then when I want to look it up again, I just search that keyword my computer. There aren't tons of options of mTNBC so my list is short...
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Thank you. I do not have that book. I will get it ASAP. Bookmarking is a great idea.
I don't understand fish how would I know if that is my cancer?
Thanks Again!
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Cure-ious, do we have a separate thread for discussing Foundation One etc results? Should we have one? I got mine back too recently...
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If there are any other threads I should be posting my questions in or should ck that would be helpful. I have a hard time finding the threads for some reason .
Thanks
Julie
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Moth, That is an excellent idea, please start one!! I only know from here that the test does not look at protein expression, just for specific protein mutations, and as more becomes known about the role for specific mutations, this could be extremely useful. also people with other similar mutations can compare therapies, yes it would be very helpful
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Kar- Oh, that would be so wonderful- I have in past six months or so had so much more skeletal/joint pain from the I-F. And yep I could take a break from Ibrance to try to "reset" it, actually might try to overlap the Femara with the Faslodex for the first month because the Faslodex degradation is not "immediate", and there is a trial testing if its better to have both at the start.
Dee- the thought is to start with a single switch (Femara to Faslodex) and scan to see if it is sufficient, and if not then switch the Ibrance to Verzenio. The main reason would be to try to keep the Verzenio for a future SERD trial, but then I see that Kar is taking it with everolimus which would also be an attractive option- the issue being that trials do not always have SERDs with any combination partner you might like
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Jjzn, I scan for news a lot and write stuff here because others would be interested but also because I quickly forget about it and so these are my notes for future reference, The reading and preparing can all go by the wayside when you face actual progression, so just post at that point your questions and the group here can crowd source a lot of help, remind you what things to check for, etc
Although there are a bunch of different ways the cancer can progress on endocrine therapy, there is only one major question- does the cancer growth still depend on the estrogen receptor or not? The estrogen receptor can mutate or work with mutated friends in a way that does not depend any longer on estrogen, but its alternately possible that other growth pathways have taken over and estrogen receptor is not used for growth, in that case neither fulvestrant nor SERDs will work. It's important to try to understand what has happened, as there are routes to try to get back estrogen receptor function- apparently in 60% of the cases they still cannot nail down the cause of progression, and its a very active area of study. A FES-PET scan can apparently resolve whether ER is still active, and in future we may just get another scan to say whether or not the Faslodex or SERDs would still work, for now just have to try it and see
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Cure-ious Thank you I did not know that. My third oncologist did tell me it doesn't matter about estrogen the cancer will just find another way. But none of my Onc have mentioned that it may not be relying on estrogen anymore. I was on verzenio after first diagnosed and had my ovaries out in November. In December my tumor counts started to rise and I had a pet scan. They told me verzenio was no longer working and moved me to Xeloda. Which didn't work either. In your opinion do you think that could be what happened? I know we get estrogen from other places too but do you think the cancer was not getting enough and switched pathways?
If I am understanding correctly you are saying it is better to get it back on estrogen positive because there are more medications to treat that correct?
Thanks
Julie
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Shout out for SERD drug ARV-471 . 🙌🏻🙌🏻
For the first time, I am classified as stable disease!! I will stay on this trial another 8 weeks and scan again.
😭tears of relief!
No new growth but there was a very slight (2 mm) increase to the index tumor which is now 3.9 cm x 2.2 cm. But this is considered a good response- the previous trial of cdk 2/4/6 had 1.2 cm growth. Big difference
Dr Hamilton was very pleased. I'm glad to have a break from researching trials/treatments for the next step. She said we can put them on a shelf for the next 8 weeks and I said I hope for many more 8 week cycles before I need a new plan! She loved that.
Dee
(Cross posting to liver thread)
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alabamaDee- I am so excited for you! I am so glad it is working. Have a lovely 8 week break in worry
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Dee- Fantastic!! Because of you, ARV-471 is in my future, and triply-so now that we see it really works!! You will be adding to the stellar numbers the drug racks up in trial. Supposedly they are opening up a phase 2 trial in second half of this year for second/thirdline patients, and one could combine it with CDK4,6 or mTOR/PI3K inhibitor- how wonderful for you to finally get to a stable place. Now Covid is receeding too and summer will soon be here!! Cue: birds singing, waves on the beach, etc
Julie, Whenever cancer progresses it is because some cells mutated and were able to figure out a way to grow around whatever drug they are exposed to. In most cases MBC starts out dependent on estrogen, then it can become estrogen-independent but still need the estrogen receptor, then it can flip over to other growth factor-driven pathways. Testing is getting better at telling us what is or might be going on, but in most cases its still unfortunately a crapshoot as to which drug to try next..
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Yay Dee! I am so happy for you. Stable is wonderful. You deserve to relax for 8 weeks and let the drugs work for you. ~Kar
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Dee,
So happy the drug is working! Are you on anything else? I tried Falsodex and it did not work for me so not sure another SERD would work?? Stable is such a relief
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Dee, did you have the FGFR1 amp mutation? Just can"t remember if it was you.
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Hi Imagine!
I'm wondering if anybody ever got a good secondline response?! Did you try Faslodex as monotherapy? Alone, the PFS in trials is 3-4 months, up to 11-12 months with a CDK4,6 inhibitor. What are you taking now?
Here is an update on Dee's drug (ARV-471). As reported below most people in the trial had been on prior Faslodex, at least one had been on prior SERDs, and they got good responses (42% made it at least six months with either stable or shrinking tumors- tho still small number of patients have been tested so far).Now Dee gets to be one of the people they can highlight, plus she has ESR1 mutant cancer, which may well go away and revert back to wild-type ER cancer after this treatment.
ARV-471 Clinical Update
As of the data cut-off date of November 11, 2020, 21 adult patients with locally advanced or metastatic ER+/HER2- breast cancer completed at least one treatment cycle with ARV-471 (orally, once-daily) in the Phase 1 clinical trial. 100% of these patients were previously treated with a cyclin-dependent kinase (CDK) 4/6 inhibitor, 71% of patients received prior fulvestrant, and 23% of patients were pretreated with investigational selective estrogen receptor degraders (SERDs). Overall, patients had a median of five prior therapies.
In metastatic breast cancer, prior treatment with CDK4/6 inhibitors predicts high tumor ER-independence, rendering ER-targeting therapies ineffective. However, one patient in the ARV-471 trial had a confirmed partial response (PR) with a 51% reduction in target lesion size as assessed by RECIST. Two additional patients had unconfirmed PRs and one additional patient demonstrated stable disease with >50% target lesion shrinkage. For evaluation of Clinical Benefit Rate, 12 patients had sufficient follow-up to be included. Five of 12 patients (42%) achieved CBR (defined as PRs + complete responses + stable disease at 6 months). Three of these five patients had previously received fulvestrant, and another was treated with two investigational SERDs.
ARV-471 has been well tolerated at all dose levels, as of the data cut-off date. The most common treatment-related Grade 1-2 adverse events were nausea (24%), arthralgia (19%), fatigue (19%), and decreased appetite (14%). None of these led to discontinuation or dose reduction of ARV-471.The phase 1 trial Dee is on is still recruiting, and they now added an arm that includes Ibrance with ARV-471.
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Dee, So happy for you! You deserve a break.
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Dear all, interesting clinical trial reviews in Hematology&Oncology journal:https://www.hematologyandoncology.net/files/2021/0... https://www.hematologyandoncology.net/files/2020/1...
Saulius
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Cureious,
Yes, I took Ibrance along with Falsodex injection from Dec 2019, had scans in May 2020 which showed improvement and stable, then around July 2020 tumor markers started creeping up and Aug scans showed progression so I switched to Xeloda and it did nothing so now on Gemzar/Carboplatin and feb 1 scans showed improvement and stability. My hope is that I can go back to gentler treatments at some point. My ONC seems to think no.
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AWESOME DEE!!! SOOO BEYOND Happy for yOU!!!
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Imagine! Definitely get some other opinions, if the MO is saying chemo is a one-way street- I was just reading a medical report about a patient who had been through a bunch of endocrine therapies (including got five months on an Ibrance-combo), then all the chemos, and then, on treatment #11, got sixteen months on Verzenio alone. All kinds of response are possible, once the cancer has mutated to escape one treament, it is now dependent on something else. We don't have the tools to say what it now depends on but if you hit the right drug it can definitely go from chemo back to targeted therapy. There are newer PARP inhibitor combos and immunotherapy combos, but you probably need to be consulting an MO involved in the clinical world to get steered in that direction..
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Cure that is great to hear bc I am about to cicle back to Affinitor and Exe....praying I get some time out of it.
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