Are you currently (or have you been) in a Clinical Trial?
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Yeah GG, maybe you DO go off of Xeloda, before the cancer becomes resistant to it, and then plan to go right back onto it if the SERD does not work or whenever you need to move to something that you know for sure will work?
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Hi, Cure-ious--
I will know by this time next week if I am still on my IO trial-- I have scans on this comingTuesday (I'll get the report as soon as the radiologist reads it, so truly I'll know by Tuesday late afternoon/evening if there's been progression or not...) but my official appointment is Thursday morning for either the start of cycle 3, or the exit paperwork and final set of trial labs.
If I don't have at least stable disease, I'll have to be ready with treatment options to consider; some will take a bit more testing/investigation on our part.
I have been HER2 equivocal (although negative by FISH) in my colon and bladder biopsies this year and last. I might try for a trial for HER2 over expressing cancers (although technically I don't met the "exhausted all options" component of this one's criteria: NCT03602079 It's at my local cancer center, so my oncologist might have a bit of influence.
There is also the DESTINY Breast04 using DS8201 for HER2 equivocal MBC also. It's at a different institution, but still in town. NCT03734029
I might re-test G360, or send a specimen of my most recent bladder bx for ESR1 mutation testing. My last G360 (in April 2019) showed a very tiny % (0.01%) of an ESR1 Y538S mutation. If it's still present I'll consider traveling to Tacoma/Seattle for an oral SERD trial (NCT 03471663), or see if a local site for a different oral SERD here has an opening (they were thinking of expanding it earlier this spring...) for RAD1901 NCT03778931
I could just say the hell with the tiny ESR1 mutation and try fulvestrant alone, even though the Y538S cancers are less-- or sometimes non-responsive-- to fulvestrant; or try to get crizotinib compassionate use from Pfizer and pair it with fulvestrant in my own version of the ROLO trial.
Of course I am hoping for at least stable disease, but given the low % of people who get benefit at this point in time from the PD-1/CTLA4 drugs, it's not likely; especially since my early biomarkers are not favorable....although the rash I developed and marked and rapid unleashing of the CTLA4 activity on my thyroid IS associated with better-than-typical response in other cancer types....regardless, I'll know shortly.
So stay tuned for a week and I'll have an update that is far more meaningful then.
I hope that there are others who have favorable reports from their trials to offer soon.
Elizabeth
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Hhmm, Elizabeth, you are in the hardest place, where you are about to see if its working or not and needing to have other good options you are happy with, just in case. Good that you are taking the two immunotherapies, which work better than one, plus adding the anti-AR receptor, but if its not working its worth finding a combo does that includes something to "unmask" the cancer from shielding immune cells.
Critzotinib would be great and there are also good (tho preliminary) reports of Venetoclax with Faslodex, most MBCs have high Bcl2...
Good luck!!!
Below link is the VERONICA trial of Venetoclax with Faslodex, phase 2- not in Portland but maybe you could do the one in Everett, near Seattle?
Interestingly this trial is also in Australia, Canada and europe, so they must be expecting a big response and hopefully will mean they get good numbers sooner rather than later...
https://clinicaltrials.gov/ct2/show/study/NCT03584...
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On the subject of venetoclax, they did a small trial combining it with tamoxifen and got a good response (clinical benefit rate 69%).
https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.1...Background: The anti-apoptotic protein BCL2 is overexpressed in ~85% of ER+ breast cancer (BC). Venetoclax (ABT-199), a BCL2 inhibitor approved for CLL (400 mg/day), synergizes with tamoxifen in preclinical patient derived xenograft models by increasing apoptosis. In the first study to evaluate venetoclax in solid tumors, we tested the safety and efficacy of this combination in ER+BCL2+ metastatic BC. Methods: A '3+3 design' dose escalation phase 1b study enrolled women with ER+ ( > 1%), BCL2+ ( > 10%, mod-high) and HER2 non-amplified metastatic BC. Patients received escalating doses of venetoclax 200, 400, 600 or 800 mg/day with tamoxifen 20 mg/day. The primary objective was to determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) over 4 weeks. There was no limit to the number of prior lines of therapy. Results: Fifteen patients were enrolled (mean age 62 years, range 44-78; previous tamoxifen, 10 pts). Mean lines of prior therapy for metastatic BC was 2.5 (median 2, range 0-6) and included tamoxifen (6 pts). ESR1 mutations were present in ctDNA of 4 patients. Treatment was well tolerated, with no DLT observed. MTD was not reached; 6 patients received the maximal planned dose (800 mg). The most common adverse event (AE) was lymphopenia (67% Grade 1-2; 13% Grade 3; No Grade 4), followed by nausea (46%, Grade 1-2), which was readily managed. Of 13 women with measurable disease (RECIST v1.1), 4 (31%) had a partial response and 5 (38%) had stable disease (clinical benefit rate, 69%). For patients with a partial response, tumor regression was rapid (evident at first restaging) and occurred in the 400-800 mg dose levels. Two patients with non-measurable bone-only disease had clinically stable disease (1 ongoing > 64 weeks). The median duration of response has not yet been reached (range, 12 to > 64 weeks). Conclusions: We demonstrated the safety of tamoxifen and venetoclax in ER+BCL2+ metastatic BC, with preliminary evidence of clinically relevant activity. A dose expansion study including serial biopsy, ctDNA and PET scans is ongoing at the 800 mg/day recommended phase 2 dose. Sponsor: Royal Melbourne Hospital Clinical trial information: ISRCTN98335443, ACTRN12615000702516.
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Hi, Cure-ious and Husband
Thank you VERY MUCH for your thoughts--I have looked into the venetoclax trial already-- their PI is very particular, and technically my bladder tumor lesion, which has very irregular edges (as do most lobular mets) does not meet RECIST criteria, so they declined me.
My onc thinks this is ridiculous, since the lesion is almost 5cm long x 1 cm wide, with the 'ruffled' edges extending at most 2-4 mm from the rest of the lesion...she took me into her IO trial with this lesion, but the venetoclax trial will not. It is a drug I would be VERY interested in adding to my regimen. Hopefully it is as effective as early results seem indicate and it will come to market in the not too distant future.
I truly appreciate your taking the time to reply. This is a great community!
Elizabeth
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Hi GG27 - thanks for mentioning the trial you are waiting for. It sounds super interesting. And maybe a way for Canadians to get palbociclib with the SERD in a second+ line setting?
I was in a trial with bazedoxifene, another oral SERM/SERD in combination with palbociclib from 2015 to 2017. Likely I'm excluded from this trial for SAR439850, but I may ask nonetheless. I'm waiting for scan results now (different trial - GDC-0077 - for last 20 months), so of course my brain is abuzz with worrying about what could be next if things don't work out.
I'm glad you are tolerating capecitabine well.
Heather
And PS - I FB messaged to your question about MBC teams at the Run for the Cure. Hopefully it's popped up?
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Thanks Heather, I answered you on FB. Stupid message requests are so hidden that you don't know someone has messaged you.
I was on Palbo on a trial so I don't know if they would give it to me again, my MO says yes, but until I actually get on the trial who knows.
best thoughts for your scan results. my next CT isn't until the end of October, a month late. I've been on trials for so long, getting everything on the exact 12th week day that I'm not used to being a "regular" patient and this whenever attitude! ha ha. My MO is on sabbatical til January so I will put up with this til then.
cheers, dee
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So the CT-Guided liver biopsy on Thursday was supposed to be day 1 of Hell Week -what I was calling a full week of pre-trial qualifications leading into the actual treatment scheduled for 9/10- but it went badly. Instead of taking core samples from one liver tumor; they took several samples from two- which added up to a LOT of liver tissue. The IR doc told my husband not to worry, that I still had a lot of good liver tissue! I think the extra tumor sample was for an ancillary study I'd agreed to. When I was in recovery my blood pressure kept dropping, so they took me back to CT and discovered bleeding in my liver. They did an angiogram to seal up any areas. Then they sent me to ER where I developed the worst pain I've ever had 9-10. If I tried to roll on my back from a position on my right side, it felt literally like somone was stabbing me repeatedly in my left side. I was screaming bloody murder and the nurse told me to "breathe." They gave me morpihne which didn't help until they gave me more much later. They kept wanting me to roll onto my back, so they could get an accurate blood pressure and or put me on the bed pan. It was brutal. One of the nurses said the reason for the severe pain is that when blood fills the sac surrounding the liver, it doesn't lessen until the blood is reabsorbed. I was there for 24 hrs waiting for a room in the hospital. I had no appetite to put it mildly and had been fasting since Wed night and ate next to nothing for days. Once admitted, things got better, but my hemoglobin kept trending downward. They kept me hooked to a heart monitor and on morphine and antibiotics and Sat they gave me two units of blood.
I was discharged Sunday, but it took all day to get out of there. Now I have to watch for shortness of breath, increased pain, fever over 101f.
Today I withdrew my consent to enter this trial. I do not want any more invasive procedures on my liver and in addition to the weekly injections under sedation, it requires another biopsy at some point.
NOPE.
I'm going to check into some standard care chemo that I haven't tried and will be open to a trial that doesn't require more invasive procedures. At this point, I don't think Y90 would be a good idea, either.
I am going to chill for the next few weeks and heal.
Traumatized.
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That sounds so terrible Kattysmith, I am very sorry to hear you went through all of that. I really hope you can find a trial or treatment that is less invasive. Sounds like they really screwed up the procedure.
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Thanks so much, Husband. I have had two liver biopsies at MDA before and sailed right through them. The same IR doc did all three.
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Kattysmith- that sounds like the scariest nightmare! I also am so sorry this happened. Sounds like they forgot the your liver was inside a living person! You are brave and make good decisions and I hope something good will be presented to you.
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Kattysmith,
Sounds like a nightmare. So sorry you had to go through that. I hope you can find something else that will benefit you better.
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UGH- Kattysmith...that was a horrible ordeal you had to endure. I'm so sorry that happened to you. I think you have the right plan for waiting a week or tow to let some healing happen before you start on another path. I hope that you are feeling better by the time you read this and that you and your onc can figure out a good next step.
I had my 12-week on trial CT scan last week, the first one on my IO trial, and holy cow, is there a LOT of progression. Bladder lesion doubled in depth, and grew 50% longer--it now covers the entire top of my bladder (It was only the left upper quadrant at the start of the trial) and I have involevement of both ureters, definite omental stranding and a bit of ascites, none of which I have ever had before...It was a lot of growth in three months. And my CA27-29 jumped from 58 to 84...And add new liver function test abnormalities-- although the CT did not show any structural hepatitis, but my AST and ALT have skyrocketed sine my last labs 2 weeks ago. It is sobering how rapidly the immune system can get triggered and start to do serious damage to our organs. The tally for this trial is, for my poor body: mild pneumonitis--at least that seems to be respolving; serious thyroiditis--with permanent destruction of my thyroid glad; mild dermatitis with an itchy lichenid rash on my flanks, abdomen, hips and sacrum; moderate pancreatitis with hyperglycemia requiring metformin; and now the hepatitis....hopefully not getting anymore of the checkpoint inhibitors will allow my immune system some room to settle down, although my onc has warned me that there can be worsening or new symptoms that appear in the months after stopping these medications.
We sent another G360 test last week and I just got the results: the ESR1 Y537S mutation has increased to 0.1% and the androgen receptor mutations (VUS, but likely inactivating) has increased to 0.2%-- I'm thinking it may be in response to the anti-androgen component of the IO trial. A previously-detected concerning EGFR exon 20 insertion has remained undetectable for these last two tests. And despite the most recent colon and bladder biopsies showing HER 2 2+ on IHC (but negative FISH) no HER 2 mutations have appeared. That makes the "low HER2" Destiny 04 trial slightly less desirable and the oral SERD trials (I am looking into 2 of them) more appealing. Now I just have to wait for my AST and ALT to drop (currently they are down from both being 6X ULN to 3 and 4 X ULN) Hopefully in another week they will have settled down into a more acceptable range for the trial requirements, and I can figure out what I am going to do. I hate this waiting...
Hope the rest of you are feeling energetic and getting good results from your treatments...
Elizabeth
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Crap, crap, crap, Elizabeth!!! I am so sorry you got bad IO side effects, and no benefit! I was also wondering about the SERDs, if the ESR number is considered high enough at this point, you need a break!!
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Hugs. It is scary that you appear to know so much about the disease and still it did not help your body being hit so hard. Hoping it will recover , lots of love xx
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Dammit, Elizabeth, that is just awful!!! I am so sorry to hear these terrible results.
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so sorry! What a bummer. I am glad that your liver is bouncing back so quickly. I hope that the thyroid replacement is an easy fix for that, but, geez! Have you looked into the crizotinib type drugs ? You’d have to get it off label. ( like ROLO trial ) etc May help ILC more.
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Elizabeth,
Just read your report on your trial. Ohmigosh -- so much going on in your body, and not in a good way. I am not going to advise you about anything, since you and your MO seem to know a lot more about this disease than I do. But please know that I am thinking good thoughts for you, for your body to settle down, and for you to find your next best treatment soon
Bev
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So very sorry to hear this Elizabeth. You have been so kind and helpful to me in the past. Wishing you the very best of luck. I don’t often visit this thread so in reading back I was so shocked to learn what you went through Katty. Hoping things will improve for you two strong brave ladies
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Elizabeth,
I don't visit this thread often but just read your report on the trial. How scary, so sorry to hear you had such poor results from your trial. I hope you recover quickly from that and can find something else that will stop the cancer from growing.
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Elizabeth, so sorry to read about what you’re going through....my best wishes for some sort of unexpected breakthrough. May you come out victorious in the end. Hugs and kisses
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EV, I hate to hear about your progression. I wanted this trial to work longer. Immunotherapy is a tricky beast and not necessarily the white horse that it is painted out to be. I had the pleasure of sitting next to a melanoma patient who has been on opdivo for 5+ years. It has saved his life so far but his life has been hard. He is constantly in and out of hospitals due to opdivo attacking his liver, kidneys, etc., etc. It sounds pretty harsh. I am interested to hear what you try next. I have the same ESRI mutation you have and am also HER2 low (2+ IHC but FISH -).
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Hi All,
Sorry for breaking in, however, we're looking for stories about clinical trial participants to shed light on this unique experience. If you feel up for it, plaase share your story for inclusion on Breastcancer.org and help others in your shoes understand what they can expect if they are exploring the option of joining/participating in a clinical trial.
Thanks so much
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Just started on a trial of Erdafitinib, Ibrance and Faslodex. Erdafinitib is an oral targeted treatment for FGFR mutation. I was eligible for the trial in spite of the fact I've previously been on both Ibrance and Faslodex which failed. There's some speculation that the Erdafitinib could help reduce drug resistance. So here we go...
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Moissy, I hope this combo works well for you!!! I am surprised that having previously taken Ibrance and/or Faslodex is not an exclusion. That is great. Do you know what dose of erdafitinib you will be taking?
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It must be that if you have an FGFR mutation, inhibiting the pathway will make the cancer become estrogen-dependent again, and therefore sensitive to I-F. Good luck, hope it works!!!
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Moissy, your trial sounds really interesting, wish they were recruiting at MD Anderson. I, too, have the FGFR mutation, have already had Ibrance (stable for two years on it) and Faslodex (which failed).
Best of luck with it and it sounds really do-able!
Katty
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Thanks for the good wishes, everyone. I was very surprised that my previous Ibrance/Faslodex wasn't disqualifying. So, yes, Cure-ious, I think they hope it can make these previously used drugs work for us again,
JFL, they've started me on 6 mg with option to increase based on labs. I know you trialed this drug also. What was your dosage? Balversa, the Erdafitinib drug just approved for bladder cancer Is being prescribed at slightly higher dosage. Katty, I hopethey expand the trial sites so you can try it!
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It's been quiet on this thread for a while...I hope everyone on a clinical trial, or contemplating a trial, is doing well.
I leave tomorrow evening for Seattle to spend all day Tuesday undergoing the last hurdles (CT and bone scans, labs, ECG) for the oral SERD trial I am trying to get accepted into. If the team of radiologists who reads the scans agree that my irregularly-bordered bladder lesion is RECIST measurable, then I should get in. As of last week, all of my labs were normal, and all of my ECGs stayed normal during my IO trial this summer, so I do not anticipate any difficulty there...
I will know by Tuesday evening if I am in, and if so, I will start at 0700 Wednesday morning with PK and other labs, then the first dose of meds, and then the rest of day 1 PK labs. Then more PK pre-and post dose 2 on day 2, and then I can go home for a week...the arm I will be in (if I'm in) is the SERD trial drug once a day with palbo 21/7 as per usual palbo dosing. It's specifically for people who had progression on pablo and an AI, and is stratified to compare those of us with ESR1 mutations against those without.
I'll check in when I know anything.
I'd love to think that you all are doing well, having good results from whatever treatment you are on, and of course, I hope each of you finds a moment of joy in your day.
Elizabeth.
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Dear Elizabeth wishing you the very best of luck getting into this trial and back with Palbo. Please let’s us know how you get on. I started cycle 40 of I/l this week so am very interested in this trial
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