Are you currently (or have you been) in a Clinical Trial?
Comments
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shetlandpony- thinking of you and hoping for whatever outcome is the most treatable. Sounds like EV11 has answered your question about testing. Im interested.
EV11- what kind of drugs are you taking for your trial?
How do you know if you are luminal A or B? I asked the UCSF second opinion doctor what I was and she said ILC is usually luminal A, but, with my progression and PR- now, I was acting more like a luminal B. Im not sure what this means.
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Thank you, Elizabeth and Nkb. I talked to my onc and she told me that now the companies just test all actionable genes across cancer types rather than a particular subset according to cancer site. And they do include MSI testing. I asked what about genes not currently considered actionable but that are of interest, perhaps because of recent research. She said if we get enough tissue she can submit it to a research study that will follow up on those.
I had the same question when the grade 1 high PR+ apparently Luminal A ILC recurred within three years with mets to the liver. My onc said, “ILC usually isn’t this nasty.” It still showed a high PR+ but if I understood her correctly, it was probably luminal B now. The ki67 was in Luminal B range and the grade was 2. For the early stage diagnosis the lab did not test ki67 so I cannot compare.
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I have two ERBB3 somatic mutations, p.V104L and p.G284R. Read about the preliminary positive solid tumor results for HER3 targeting ADC, U3-1402 developed by Daiichi Sankyo Pharmaceuticals. But having ERBB3 somatic mutations doesn't mean that I have HER3 receptors, right? As with HER2 receptor status that is identified by an IHC test, is there an IHC test for HER3?
Here's the preliminary report: https://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/007023.html
On the other hand, there is this trial of Neratinib for ERBB mutation-positive or EGFR gene-amplified solid tumors: https://clinicaltrials.gov/ct2/show/NCT01953926
Hugs, Susan
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Susan- nice to hear from you. What treatment are you currently doing? And how are you
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So I'm kicked off the BYLIEVE trial due to a small amount of progression on one liver spot, but I knew they wanted me off the trial last cycle. I've been put on a very low dose of Xeloda, 500mg 2x per day for 14 days on/7 days off. Because I had a bad reaction to the alpelisib my MO wanted to start low & work up if need be.
Someone was asking what next trial I was considering (Theresa, I think) This is the one, "A Phase 1/2 study for the safety, efficacy, pharmacokinetic and pharmacodynamics evaluation of SAR439859, administered orally as monotherapy, then in combination with palbociclib in postmenopausal women with estrogen receptor-positive advanced breast cancerBCCA CODE: BRTSERD (on hold as of 1May2019)"
My MO wanted me on this but it's delayed until probably November which is too long for me to be on nothing, so low dose Xeloda it is.
cheers, dee
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GG27- so sorry about the progression and I hope the low dose Xeloda keeps you stable until your trial
What is SAR439859?
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GG27 - I'm sorry that you've progressed on Faslodex and been kicked off the BYLIEVE trial. I was the one who asked which oral SERD trial you were considering. Thanks for the info! It's interesting to me that the SAR439859 (oral SERD) trial will include Ibrance. It makes sense that oral SERD developers would want to see if their oral SERD can increase response to Ibrance. It's great that being previously treated with Ibrance does NOT exclude you from the trial. My trial is a monotherapy of the G1 Therapeutics oral SERD (G1T48). I have an RB1 loss mutation (rare in ER+ breast cancer) which predicts that CDK4/6 inhibitors will not work for me. I tried Faslodex/Ibrance for 4 months and, as expected, it didn't work at all. I do wish that the oral SERD I'm taking could be paired with Pqray or Afinitor to give it a better chance of working... I hope that you get a long and gentle side effect run on Xeloda!! Many people have had great success with Xeloda. The Xeloda thread is filled with lots of very useful information and supportive ladies.
Theresa
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Dee, I'm sorry you got the boot from Alpelisib, but OK, we move on to better things! The time you had on the drug nevertheless affected the cancer, and may help it be more responsive to CDK4,6 inhibitors when you try them again in the future. I see your trial listed online, but it just indicates "recruiting" even in Vancouver and Toronto- is the delay because your local trial site already has the max number of patients? Or is there some systemic problem and they are delaying the trial at all sites?
I like the SERDs, and theresa it will be so interesting if you respond to SERD monotherapy!! Supposedly they are much stronger than Faslodex, so will be a stronger endocrine inhibitor than any of us have had. How far along are you in the trial, and what about SEs?!
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Cure-ious, I've been on the trial for 2 weeks. I've had almost no SEs, other than a little indigestion. I have a bit of fatigue, but I think that's left over from the liver resection I had 5 weeks ago. At my two week appointment, it looks like a visible bump on my sternum has continued to grow, but it's too early to make a judgement about whether or not the treatment is working. I will have tumor markers drawn at 4 weeks (not part of trial) and scans at 8 weeks (requirement of trial). It would help so many of us if the oral SERDs can circumvent hormone resistance (eg, ESR1 mutations)! Mine is a phase 1 trial, so it's still dosing and proof of concept in humans... Theresa
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Cure-ious, the trial is delayed due to paperwork according to my MO & trial RN. There aren't any patients on it yet as it isn't recruiting yet in Vancouver otherwise I would have been on it. Not sure why it shows it is, but on the BCCA Vancouver site it shows "delayed" They are saying November to me. If Xeloda is ok for me, I would be happy not to be the first guinea pig anyway. It didn't work out well for me last time. I feel like they put me on the drug that potentially has a lot of bad SEs with no solutions & alot of barriers. They now allow all kinds of things to help with the SEs that I was told I couldn't take on the trial.
Theresa, good luck with the trial, continued few or no SE's.
It's a lovely day here on the west coast so I'm going outside to enjoy some dirt therapy! Happy Sunday all! cheers, dee
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Nkb-
I am on a Nivolumab/Iplibumab/bicaluatmide trial (anti PD-1, anti-CTLA4, androgen inhibitor)...I have just completed cycle 1 (for this trial a cycle is 42 days, ipi/nivo Day 1, then nivo alone day 15 and day 29, with 150 mg bicaluatmaide every day. Cycle repeats every 6 weeks.)
I have a CBC, CMP, LDH, Mag and Phos, and 7 vials of trial labs every two weeks; I'll have tumor markers (CA 27-29 and CA15-3) dawn at the start of each cycle. Interestingly, my CA15-3 drawn on day 1 was normal (28) but my 27-29 elevated (58); in the past I have only had 27-29 drawn, and it is always elevated to some degree...it will be interesting to see if CA 15-3 remains normal or changes over time. CBC and CMP, including liver function is normal so far. I am having minor fatigue, and daily feelings like I am about to get a cold (burning behind my eyes, fullness in my ears, slight sore throat, minor aches-- all from immune activation, I imagine) and a mild lichen-type rash on my sides, abdomen and sacrum. I'll have scans at week 12, I believe. So far it's pretty easy besides the minor side effects, but we are watching out for auto-immune side effects, which can appear at any time and be serious or even fatal.
My labs are indicative of good response in 2 of 4 ratios that they are interested in (LDH and dNLR --derived Neutrophil to Lymphocyte ratio) but indicate of a poor response in two other values: LMR -- lymphocyte to monocyte ratio and absolute lymphocyte count.) So we will see how it pans out in the end. If I need to move off this trial in the near future I am looking into an oral SERD trial or trying to get crizotinib off-label to use with fulvestrant, despite the ESR1 mutation I have developed. It was only detected at 0.1% cfDNA, and there is a chance that over time, off estrogen suppression (it will have been at least a year of no anti-estrogen therapy by the time of my scans) that those clones might have been eliminated.
I'm grateful to have the chance to participate in this immunotherapy trial, even though I know that only 8-13% of patients in other two trials have a CR, and another 18-20% have stable disease-- so two thirds have no benefit. But I'm hoping that it keeps me stable for a while. I've never been NED in the 4 years I've dealt with MBC, and I'll be overjoyed for a stable response.
Day 1 cycle 2 is July 26-- I'll post more than.
Hope you all are tolerating your treatments well, and find a moment of joy in each day.
Elizabeth
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EV, I find it so interesting that you can detect the buzzing of a hyperstimulated immune system!!
Do you have detectable PDL1 expression or high tumor mutation burden that would pre-dispose you to respond to immunotherapy? Obviously our immune systems are killing off tumor cells daily, so that part is enhanced, I guess the question for the scans is if there is now a qualitatively distinct ability to get it and wipe out tumor masses. Good luck!!
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Cure-ious-- earlier testing for PD-1/PD-L1 did not reveal high expression (although I did have 1-3% PD-1 on one tissue sample--initial peritoneal mets-- earlier in my course)....TMB is 11, so intermediate. I do have pleomorphic ILC, and a lobular-knowledgeable researcher (Christine Desmet) has told me that in her limited experience looking at the immunogenicity of lobular samples, many of the (admittedly few) pleomorphic specimens she studied had significant TIL in the tumor and microenvironment and she believes that pleomorphic may have a better than average MBC response to IO. We will see if this "n of 1" bears that out...
I greatly appreciate your well-wishes! I'll keep in touch as I learn more. This afternoon I am suffering more than I have from some of the side effects; I hope that it settles down before C2D1. I'm not sure what their criteria is for holding infusions and/or investigating autoimmune activation. But I definitely feel more "off" today than I have to date.
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EV11- I have pleomorphuc ILC also- I was told by two MOs, one from UCSF that my cancer is “garden variety “ and the pleomophic doesn’t mean anything. I hope you friend is right and this really works well for you.
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wasn’t sure where this might go, but i found it exciting:
https://newatlas.com/vaccine-supercharges-cart-cell-cancer-therapy/60550/
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Wow!! OK, I am holding out for this, what would you call it? Revved-up CART?
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I would call it fantasyland....but that's me..you should see the look on my mo's face, a major researcher at MSK, when the topic of immunotherapy for breast cancer comes up...
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CROSS POSTED..
Help! Just looking for some guidance as I am basically clueless. Recent Guardant360 blood test results:
Alteration % of DNA or Amplification Associated FDA approved therapies Clinical Trial Availability
ESR1 D538G 0.04% Fulvestrant Yes
TP53 A159P 2.5% None Yes
TP53A151G 2.4% None Yes
The list goes on with other TP53 letters/numbers but all are at or below 0.2%. I asked onc what the super low percentage on the ESR1 meant and she said she didn't know but had reached out to the company to ask. She is tentatively recommending a trial of oral Fulvestrant and Femara/Ibrance or Aleseritib/Faslodex (not sure if spelling is correct.
First line treatment was Faslodex and Ibrance for about 38 cycles. Some progression in ribs so she switched to Affinitor/Aromasin. Been on that regimen since late October 2018. Recent scan indicated mild abdominal ascites, but this problem is worsening daily and I have an US scheduled for August 1st. As of now, I am still considered bone only mets.
Looking for any info on the Guardant blood test as well as your thoughts about my abdominal ascites/tenderness/pain. This is also from the CT report:
Abdomen / Pelvis: Physiologic FDG activity is identified in the
genitourinary tract and bowel. Small foci of air in the right pericolic
gutter is favored to represent intraluminal gas. There are thickened loops
of small bowel in the lower abdomen (image 177), concerning for enteritis.
No metabolically active abdominal or pelvic lymphadenopathy. No
intraperitoneal masses. Small volume ascites is new from prior. Anasarca.I take Lasix daily for fluid buildup but no relief in the abdomen......
TIA for your feedback and hope everyone has a great day!
MM
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masonsmawmaw-
It sounds like you have lobular mets to your peritoneum and perhaps in your colon, even thought he radiologist doesn't use those words to describe the findings-- but the radiologist's description is classic for lobular mets in those locations. You might want to consider a colonoscopy with biopsy of any lesions to see if you get any additional mutational information from that (see if ESR1 % is similar or not; or if there are other actionable mutations that are present that aren't detected in the G360 blood test.)
I have a great article about colonic lobular mets for you to give to an endoscopist if you decide to do the colonoscopy...I shared it with my GI doc who had never heard of lobular mets in the colon- he read the article before my colonoscopy and asked me some questions via email before it-- I told him to have a high degree of suspicion if he saw small flat lesions and to grab a number of them if he saw them-- he did indeed see about 2 dozen 1mm-6mm lesions scattered throughout my colon-- he biopsied 11 of them and 9 were lobular mets. Two small lesions were normal colon mucosa. He said he had never seen anything like it before, and since the surrounding tissue did not seem inflamed or vascularized he may not have been overly concerned by them. We were both glad I had shared the article with him. Send me an email at eav.pdx@gmail.com if you want me to send the article to you.
Regarding your 0.04% ESR1 mutations-- I had G360 test a year ago that found a 0.01% EGFR mutation that is known to be highly aggressive--I called the G360 geneticist who was LOVELY, patient and very informative. She told me that 0.01% was the smallest detectable concentration that they could detect; that mutations present at less than 0.1% may not be clinically relevant, since sub-clones present themselves and get eliminated very frequently either through therapy or by our immune surveillance about as often as they grow to establish significant metastatic colonies. She suggested that I undergo whichever treatment I was considering without focusing too much on the EGFR mutation in particular and see how that mutation fared in a repeat test in 4-6 months...I re-tested at 9 months for a variety of reasons and the EGFR mutation was not detected anymore. Nor was it present in another test about a year later. So I might be clinically significant, or your body may eliminate it...
The combined % of your TP53 clones may be more concerning- if I were near a clinical trial for a med designed to attack TP53 mutations, or if I could travel to one relatively easily, I would seriously consider that. But if not, an oral SERD trial would be appealing to me, or even fulvestrant with or without alisertib might be worth a try for a few months.
Please let us know what your oncologist learns from the G360 person--and please keep us updated with what you decide to do.
Elizabeth
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Yes, Frisky, it IS FantasyLand, with clinical trials starting in a year!!
The paper shows they got 60% elimination of solid tumors in mice when using the booster vaccine+CAR-T, compared to no loss of the solid tumors with CAR-T alone!!! And they re-challenged the mice with cancer twice and the engineered T cells protected both times. This could be a game-changer for CAR-T in solid tumors, and I really didn't expect to see something make CAR-T work on tumor masses in my lifetime...
We need a name for this technique- how about Super Mario CAR-T?
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Skyfly, interesting article. Gives me hope. I think that many of these unsuccessful treatments may require nothing more than a small adjustment to work. I hope that is the case here!
Cure-ious, Super Mario CAR-T it is!
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Love that Cure-ious!
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What do y’all know about Lasofoxifene? I read an article about getting the FDA to fast track it, but I’m really not sure what this means? How fast is the fast track?....and will this potentially replace Faslodex and Zometa/Xgeva?
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I love that explanation, graphic and the nickname you've chosen Cureious!
I hope that like those mice, we all get to benefit from those super charged Mario Cart-T therapies!
I suspect now, that the look on my Mo's face is one of envy
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EV11- Thanks for the insight you have provided although I must say I am absolutely floored at even the remote possibility of lobular mets! I am going to send you an email so that you can send me the article you mentioned. I must say that my MO is not very forthcoming with information; I really don't know if it's just that she doesn't know, or if she assumes that I already know but I am so incredibly confused by mutations and everything else in general regarding my cancer. Even though I've battled cancer many times (kidney in 1969, breast in 2001, thryoid in 2011, recurrence in bone in 2015), I've just always sort of went with the flow and did whatever I was told to do. Now, since joining BCO, I find that so many of you are much more knowledgeable than my MO in terms of treatments, etc. Can you tell me exactly what the ESR1 mutation means? And what about the other 7 TP53 alterations? What does that mean?
I appear to be eligible for a trial at UNC for GIT48, an oral SERD. My MO also mentioned Aleseritib/Faslodex or Verzenio. What are your thoughts? I should also mention that I have generally poor kidney function (only one kidney) and was diagnosed with cardiomyopathy in 2010 from use of "red devil" in 2001. I have a defibulator/pacemaker. I would not take anything with known or possible effects to the heart.
My abdominal ultrasound is still scheduled for August 1st, but I'm trying to get it moved it since your comments scared the bejesus out of me....
Will advise as I know more. Hate to be a pest in asking these questions, but again, such a wealth of information and knowledge on this site helps ease my mind....
Have a great weekend everyone!
MM
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Masonsmawmaw - I have been on the Phase 1 G1T48 (oral SERD) trial at Stanford for almost 3 weeks. I have an ESR1 mutations which predicts that aromatase inhibitors (AIs) are unlikely to be effective against my cancer. I am currently on 800mg/day of G1T48 and my only side effect is acid reflux/indigestion with mild nausea. I just started taking zantac for the acid reflux which seems to help. On the phase 1 trial, they are trying to determine the optimal dosage in humans from both a side effect and efficacy perspective. The first patients started on 200mg/day and the trial will continue to increase dosage up to 2000mg/day. I started on 800mg/day and have been given the option to increase to 1000mg/day next cycle, which I will do. The trial calls for scans at 8 weeks, so I will have more information on effectiveness in 5 weeks (although only in my cancer). I'm not aware of any kidney or heart issues with G1T48; however, the trial did require baseline EKGs at the start of treatment. Very best wishes in making your treatment decision!! Theresa
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How is everyone doing in their individual trials?
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SandiBeach and others--
I started the second round of my Nivo/Ipi/Bicalutamide trial last Thursday...my labs still show a mixed response, leaning more towards the "indicative of a poor response" category than of a good response, but I am completing cycle 2 (6 week cycles) and I will have a CT scan the first week of September.
I have developed an autoimmune thyroiditis-- I am severely hyperthyroid. My TSH dropped in 2 weeks from 1.06 to 0.01! Apparently this is an uncommon but known side effect of these I/O drugs; almost everyone who develops thyroiditis will go on in a few weeks to have their thyroid permanently destroyed by autoantibodies...so I will be permanently hypothyroid. In the grand scheme of possible autoimmune side effects from these IO meds, this one is relatively minor---I just feel pretty crappy right now in the hyperthyroid phase....it should only last 3-6 weeks, then I will start thyroid replacement medication. If it isn't one thing....
Am trying to stay optimistic, but also contemplating my next options if I have definite progression in Sept. I had a small % (0.01) of mutant ESR1 (Y537S) cfDNA appear in my last G360 test-- I may repeat the test and see if that has changed, or if any new actionable mutations have appeared. Might try for an oral SERD trial in Seattle (3 hours away) since the Y537S is not very responsive to fulvestrant. Or I may petition Pfizer for crizotinib off-label and pair that with fulvestrant. Otherwise I'm not aware of any other viable options. That damn ESR1 mutation has knocked my option of trying exemestane (I've only bee on letrozole.)
I'd certainly appreciate any suggestions from you bright and supportive women!
Hope you are busy enjoying a fabulous summer!
Elizabeth
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EV11 –Thanks for the update on your trial experience. I'm praying that you will see a good response in September despite the mixed lab results. I'm sorry that you've developed autoimmune thyroiditis and hope you will not experience any other IO side effects!!
I'm in my second cycle of the phase 1 G1T48 oral SERD trial. They bumped my dosage from 800mg/day to 1000mg/day for the second 28 day cycle because other patients have tolerated the higher dose well. The trial will increase dosages in each consecutive starting group until they hit unacceptable toxicity or reach 2000mg/day. On the phase 1 trials, you know that you will get the drug, but since they are trying to find the optimal dosage, you do not know that you personally will receive enough of the drug to be effective. I have some acid reflux, but no other side effects. My tumor markers rose significantly (40% increase) at the 4 week mark, so I'm also, as you so perfectly stated, "trying to stay optimistic while contemplating next options." I also have a sternum/skin met that may be increasing and certainly isn't shrinking. The trial calls for 8 week scans. I'm scheduling radiation to my sternum/skin met, so the radiation planning scan will provide an early peek into whether my cancer is responding.
Some thoughts on your next treatment. Your ESR1 percentage is very low, so maybe exemestane or faslodex in combination with another treatment could still work for you. For comparison, my ESR1 (Y537S) mutation is 2.3% on Guardant360. Are you HER2 equivocal? If so, the Daichi DESTINY-B04 Trial of DS-8201a in HER2-low patients could be an option for you. I'm considering that trial.
Very best wishes! Theresa
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I've been in my immunotherapy trial since December and have had a fantastic response (44% decrease in target tumors), until now. Yesterday was my last day in the trial because of an increase in size and number of my liver tumors. Progression showed up in my June scans, but they were hoping it was psuedo-progression, so I was allowed to stay in the trial until my scan this week confirmed more progression. My two largest hepatic tumors increased from 2.2 x 2.4 cm to 3.3 x 3.4 cm and 2.5 x 1.8 cm to 3.2 x 2.3 cm. and I have several smaller diffuse (correct term?) lesions. Other non-liver nodes have minute progression or remain stable.
So I'm at a crossroads. My gut tells me to get a referral for an IR doctor at MD Anderson to see if I'm a viable candidate for Y9, because unless I do something that is proven in many cases to slow progression in the liver (I've been following the Y90 etc thread for months), I'll be looking at liver failure in *several* months. My liver values are all good as is the rest of my bloodwork and general health. In conjunction with or after both lobes are done, I could try another convention systemic treatment to keep the hounds at bay.
BUT, my study doctor offered another Phase 1 immunotherapy trial which in my panic I consented to, but can withdraw at any point. Dr. J doesn't know why my initial trial started failing after months of success. I am the only patient in his trial who had such a good response. He postulates that my tumors may have become *cold* and therefore unrecognizable to the immunotherapy drugs. This trial would stimulate inflammation (making them *hot) in my largest tumors which would then theoretically spread to other tumors making them more succeptable to the immotherapy. Here's the short form: Preclinical Characterization of BMS-986299, a First-in-Class NLRP3 Agonist with Potent Antitumor Activity, Alone and in Combination with Checkpoint Blockade
It's a pretty hairy, invasive regime for my liver. Once a week for 5 weeks, I would have the study drug injected directly into my liver tumor. It would be treated like a liver biopsy with conscious sedation and a SIX hour recovery with possible overnght stay in case of fever. He would scan me after a month and at that point, if my tumors looked receptive, he would add Nivolumab (which I've been on) and Ipilimumab (which I know nothing about yet. I'll be up there a minimum of two-three days per week for 5 weeks and unless I bail out before, I'll start the first week in September.
I always have questions AFTER my appointments, because it takes a while for things to percolate with me. If you have any suggestions of questions to ask or any thoughts on what direction you think I should go, (Y90 + conventional or trial ) please chime in! I feel like things are happening too fast and I want to make the most informed decision I can. And, it just figures, my former MO prior to the clinical trial is leaving MDA early next week, so I won't have him to bounce these ideas off of.
I don't rattle easily, but I am well and truly rattled right now.
I'm crossposting on Y90 thread and my clinical trial thread.
Thanks to one and all,
Katty
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