Elacestrant (ORSERDU)
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After several phone calls this morning, between my doctor's office and the specialty pharmacy Onco360, Elacestrant (Orserdu) has finally been scheduled for delivery on Wed. I hope to start Thurs AM. I start at the usual dose of 345mg 1x day. Dose reductions are possible. I need to call my doctor's office again to get baseline labs ordered. Based on trials, Elacestrant can affect triglyceride level (30%), liver enzymes AST (29%), ALT (17%), Sodium (16%), Hgb (26%). Makes me nervous. Other side effects are nausea, vomiting, fatigue, muscle aches, diarrhea or constipation. The women on this drug, who post on the Facebook group, report a wide range of side effects. The median Progression Free Time is 3.8 months, but again there is a wide range of outcomes for the women on the Facebook group. I think it makes sense for me to try this treatment before moving on to Enhertu.
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@weninwi - Best of luck!! Elacestrant was the easiest drug for me in terms of side effects. I felt the best I had in years. I monitored the FB group when I was on Elacestrant, and I was surprised by the wide range of side effects. I think I had a little nausea the first month (did not take anything) and my lipid panel seemed to be ever so slightly affected. I wish you the best.
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Cure-ious,
I wonder if the percentage of the ESR1 mutation, prior to starting Orserdu (elacestrant), might be a factor in the response to treatment? My percentage was 30% based on solid tumor biopsy genomic test by STRATA. Some women on this treatment, who share on a private Facebook group, have indicated they have less than 1% mutation. Apparently the drug company that makes this new SERD set a level of 1% or greater, but I don't think the percent has to be reported to qualify for treatment. As I read the Emerald Study results, women who have the ESR1 mutation had longer PFS than women who did not have the mutation. Based on your professional experience, do you think the percentage of ESR1 mutation might be a factor in the response to treatment? Thank you.
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Hi WeninWI!! well, like you I have been wondering what the the prevalence numbers mean for response to a drug, it really hasn't been discussed much elsewhere. Given that levels as low as 1% are enough to qualify for Enhertu, 30% sounds like a lot! In addition, they say that the PFS numbers for Elascestrant were also higher for those who responded well to a CDK4,6i, so maybe that may signal that you would get a longer time on the drug. With that high a level it would seem like you want to get rid of the ESR1 mutation regardless of what treatments come next, otherwise it will just continue driving the cancer growth because the mutation lets it do so even in the absence of any estrogen, and you aren't doing anything to block it. Once treated with elascestrant, it will be degraded and will not be selected for, so at least that avenue will be shut down.
But then what else can you add? The goal would be to block whatever other pathway the cancer would try to use to grow in spite of the Elascestrant. Clearly CDK4,6i are out because the CycD amplification means the cancer has gained resistance, but what about taking things to block the PI3KCA pathway, which can be turned on by PI3KCA mutation but also by a lot of other things in the cancer, like things that activate the AKT kinase. Do you take a statin? I take Livalo (pitavastatin), which has a strong anti-cancer activity and does not use the Cyp3A degradation route, so has fewer drug interactions. Among the activities it has beyond cholesterol reduction, it is a potent inhibitor of Akt, which is not only a main driver for the PI3KCA pathway but can also be turned on by various other cancer genes. In addition, statins often synergize with Celebrex (celecoxib, a prescription NSAID used for arthritis pain). Celebrex inhibits the COX2 enzyme, which is induced by PI3KCA, and can also help inhibit resistance to Pi3KCA inhibitors by blocking PDK-1. In addition, Celebrex has some inhibitor activity to CDK2, and it has often been seen that statin and NSAIDs work synergistically together. And these do have effects at normal drug doses, eg Livalo is in clinical trials at the 2mg dose, which is the middle of its normal doses.
And I think further testing by blood biopsy and liver biopsy becomes really important after this step. It gets harder to guess how the cancer will change- will it gain Her2 expression, for example? Will the CycD amplification stay or go away, and if it goes away, would the cancer then regain sensitivity to CDK4,6i? Also, what is the tumor mutation burden? I read this number normally does not change but can go up after treatment with CDK4,6i, and if its goes up, it indicates the cancer has become more sensitive to immunotherapy. And only a tissue biopsy can give information about ER, PR, AR expression, etc…
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Cure-ious,
Thank you so much. Your first paragraph seems especially applicable for me to grasp right now. Last Aug, when I had the liver biopsy genomic test, it showed I was negative for ATK, ATK1, ATK2, PIK3CA. My AR was high at 15.0. I have a video appt with my Mayo second opinion MO this Fri, so I'll work on some questions. She has been more forth coming with information that my regular MO. One question I will ask is when would she recommend repeat genomic testing? Would she recommend solid tumor or liquid biopsy?
My MO has ordered a lipid panel before starting the medication. My cholesterol from last fall, when I was on Afinitor, was mildly elevated at 259. I've never had a conversation with any doctor about statins and not sure I would be interested. But the information you provide is interesting. And I don't have arthritis pain, so Celebrex has never been discussed. I will start the treatment either Thur or Fri. Thanks again!
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Wonderful to get a second opinion, and does it suggest that Enobosarm could be useful in the future, given the high AR? And please ask her if the different prevalence numbers (%) have a meaning in terms of treatment- for example, what is the minimum level of detection of ESR1m that would justify going for a SERD? And even would it be better to wait for a low % ESR1m to get higher before starting a SERD? I can't find anybody commenting on that…
PS To clarify, the statin and NSAID considerations are for those cancers with PI3KCA mutant or hi-Akt cancers, not for those only with ESR1m, which can be treated well with the oral SERDs
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My first bottle of Elacestrant (ORSERDU) arrived and I will start tomorrow. Elacestrant is a new hormonal therapy known as a SERD (Selective Estrogen Receptor Down Regulator). I printed off and read over the prescribing information from on-line. On page 2 it says it should be "taken orally with food once daily". On page 8 there is an statement about Effect of Food: "Administration of Orserdu 345mg with a high-fat meal (800-1000 calories, 50% fat) increased Cmax by 42% and AUC by 22%, compared to fasted administration". A retired pharmacist friend defines Cmax and AUC as follows: "Cmax is the peak concentration a drug reaches while “area under the curve” describes the total amount absorbed. With elacestrant, a fatty meal increases the amount you get, partly by adding absorption time which maximizes the blood level". I take all this to mean, bottom line, take the drug with biggest meal of protein, carb, and fat.
On the private Facebook Orserdu group it is also recommended to drink lots of water to flush dying and dead cancer cells (the cellular debris) out through the kidneys. How physiologically accurate this is, I don't know, but at least it's a hopeful expectation and easy intervention.
Had new baseline bone scan today. My MO said since I had progression in the liver on CT scan Aug 9 and I will be starting new treatment with Elacestrant, she wanted a new baseline bone scan. Results: "No new lesions suspicious for osseous metastases". I'm so relieved and thankful.
Median PFS for elacestrant is 3.8 months, but have found this reference:
https://ascopost.com/.../emerald-trial-elacestrant-vs.../...
Among the ESR1-mutated population, progression-free survival was also improved with longer prior exposure to CDK4/6 inhibitors. In ESR1-mutated tumors and with at least 18 months of prior exposure to CDK4/6 inhibitors, median progression-free survival was 8.6 months with elacestrant vs 2.1 months with the standard of care, a 53% reduction in the risk for disease progression or death. Results were similar in those with ESR1-mutated tumors and at least 12 months of treatment on CDK4/6 inhibitors. For those with ESR1-mutated tumors and at least 6 months of prior treatment with CDK4/6 inhibitors, median progression-free survival was 4.1 months vs 1.9 months, respectively.
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Two members on the private ORSERDU Facebook site have recently reported they have had liver progression and will be moving to a new treatment. Not very encouraging.
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Had a second-opinion appt with my Mayo Clinic breast oncologist. I'm so thankful that I've been able to continue these appts. I asked about the 10% bioavailability of ORSERDU and improved absorption if the drug is taken with a high calorie, high fat meal. She said to focus on the study results…..i.e. that the drug worked especially for women with the ESR1 mutation…rather than on the pharmacokinetics. Not the answer I was hoping for, but at least she answered. She also said she didn't think the percent of the ESR1 mutation (mine is 30%) mattered in terms of response to treatment, as long as it was 1% or greater. I plan to continue to take the drug with a high calorie/high fat meal, which for me is breakfast. Took second dose today.
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weninwi- Thanks, its good to know that mutations over 1% in genomic testing are considered valid and worth targeting. No reason to wait for them to become more prevalent.
some more stats from Elascestrant trials:
Head-to-head with fulvestrant, patients given elacestrant had a higher PFS at 6 months than those on fulvestrant, at 34.3% vs 22.9%; and at 12 months it was 22.3% vs 10.2%, respectively. What’s driving the clinical utility of elacestrant is the fact that at 6 and 12 months there is a substantially higher chance of being progression free with elacestrant compared with fulvestrant. By comparison, Giredestrant did not show better activity than Fulvestrant (and yet is still in clinical trials for combinations) and Camizestrant did much better for than Fulvestrant, regardless of ESR1m. Food doesn’t interfere with the absorption of the drug and its mainly recommended because it decreases the nausea. Furthermore, if your patient’s on a proton-pump inhibitor (PPI), that’s OK. Elacestrant was given at 400 mg on the trial schema, but as it turns out the pill is now given in a tablet of 345 mg, so starting with somewhat less drug. You start with the 345-mg tablet given with food, and if you need a dose reduction, you can take 3 x 86-mg tablets, or if needed try 2 of the 86-mg tablets. But most patients did not need to ask for dose reduction.
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@cure-ious - FYI - I believe the trial 400 mg and the current 345 mg are actually equivalent doses. When I first started elacestrant, it was confusing to me. I found in the dosing info somewhere that elacestrant 345 mg is equivalent to 400 mg elacestrant dihydrochloride (which is what the study had). I had early access to elacestrant and received some of the vials that were used in the study, so they were labeled as elacestrant dihydrochloride.
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oh, that makes sense now! thanks…
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I'm on Day 6 and no side effects. The drug package insert says "Steady state is reached by Day 6". Steady state refers to maximum concentration.
I received a call today from Optum Specialty Pharmacy to tell me they received a forwarded Rx from Biologics Specialty Pharmacy, but Optum says they do not carry this drug. I explained the Rx was already filled Aug 18 by Onco360 Specialty Pharmacy. I then called Biologics immediately and they say there is nothing in their records that show they forwarded a prescription to Optum. Getting this Rx filled has been one confusing situation after another.
I also received a phone call today from an Onco360 nurse to ask how I'm doing on the drug and to give tips on how best to take it. Taking with a big meal to reduce any nausea and vomiting was encouraged. I've had no nausea so far. Drinking 6-8 cups of water per day was encouraged. This nurse also mentioned increased skin sensitivity due to sun exposure, so should take precautions. I do not see this skin side effect risk mentioned in the drug insert.
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This article was posted on the private Orserdu Facebook group site:
It gives a good summary of how Elacestrant works, etc:
"Orserdu will be available as 86 mg and 345 mg film-coated tablets. The active substance of Orserdu is elacestrant, an anti-oestrogen endocrine therapy (ATC code: L02BA04). Elacestrant selectively binds to oestrogen receptor-α (ERα) and degrades ERα protein, disrupting ERα signalling and thereby inhibiting the growth of ERα-positive breast cancer cells, including those harbouring oestrogen receptor 1 (ESR1) gene mutations."
"The benefit of Orserdu is an improved progression-free survival (PFS) in patients with ER‑positive, HER2‑negative advanced breast cancer with an activating ESR1 mutation who had relapsed after at least one prior endocrine therapy in combination with a CDK4/6 inhibitor, when compared to standard of care."
"The most common side effects are nausea, increased triglyceride and cholesterol levels, vomiting, fatigue, dyspepsia, diarrhoea, decreased calcium, sodium and potassium levels, back pain, increased creatinine levels, arthralgia, constipation, headache, hot flush, abdominal pain, anaemia and increased alanine aminotransferase levels."
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Hi all,
I read all your posts and gained a lot of learning from you all, thanks for sharing.
I have progression on my primary tumor and some activity in my liver in the last scan. apparently I have ESR1 mutation as well as NF1 which is way too higher than ESR1 and GATA3 gof, as reported by Tempus. they couldn't complete the study due to insufficient tissue sent by my current clinic, so the BTM burden for immunotherapy cant be reliably determined. I've searched and read many articles but I am now more confused.
the next scan is scheduled for next week, and hopefully I will be able to get a second opinion a week after. but for now I want to explore my options before I meet with the second opinion and my MO. please share any comments/ideas which treatment should be considered first? Elacestrant or immunotherapy or something else?
Thnxxxx
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snow-drop,
The Orserdu discussion board does not have many active commenters. I've been making most of the posts lately in an effort to document my learning and experiences with the drug. Commenter "cure-ious" is probably the best commenter to respond to your question. She usually posts on the "Are you currently (or have you been) in a Clinical Trial" topic. Suggestion: I think it would be helpful to anyone making any treatment suggestions if you completed a Disease and Treatment history under your signature.
If you end up on Elacestrant (Orserdu), the most active site, right now, is a private Facebook group. You must be on the drug to join. I prefer the quality of BCO, but with few participating on this Orserdu discussion it has limitations.
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Thanks weninwi, I didn't know my signature disappeared, fixed it now.
Hi @cure-ious I would appreciate it if you could comment on this issue, ESR1 gof and NF1 lof and GATA3 gof mutations reported by tempus. I have been on my first line of treatment hr+ her2(+1), letrozole+ibrance+xoladex and xgeva for about 3/6 months, recent scan showed a small activity in my primary tumor which assuming a progression. In this article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286719/
my understanding is NF1 lof mutation seem to have dual pathways for driving breast cancer, which without working on these 2 together, a SERD treatment might not be as effective. so the authors suggest a combination of MEK inhibitors with SERDs. if you have information on any research or trials please share. Thank you
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snow drop, Have you considered removing the primary tumor?
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Thanks Cure-ious
I do want to remove the primary tumor and I have been in ongoing discussions with my MOs about this, so far they have disagreed. it is actually one of my concerns, I will definitely discuss it with a second opinion.
I'd like to know your opinion about removing the primary tumor, especially now.
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WeninWI, Bone-only mets were allowed in the Elascestrant trial, but I can't find how that subgroup did- do you (or anyone in the Facebook group) know about that?
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cure-ious,
The commenters on the Facebook group mostly report on their own experiences. They do share if they are bone only or bone plus viscera, but they don't quote studies much. I visit the site most every day and my sense is that a good number of those with bone only are seeing a good response - either stable or shrinking. Some interesting aspects of what these women report: a good response seems to develop slowly so they are encouraged to keep on treatment until 2nd scans at 6 months, tumor markers tend to rise before falling, so they are encouraged not to panic. I've been paying attention when mutation percentage is shared - It's a wide range: quite a few are <1% up to highs like 14%, 21%, 35%, 37%, 43%. The most reported side effects seem to be bone pain; severe gastric reflux if pill not taken with enough food, fat and water; and fatigue. Some women are tolerating it well with little to no side effects.
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Thanks, WeinWI, I intend to ask my MO tomorrow about switching from Fulvestrant to Elascestrant, not sure if it would be "strong" enough (given its just monotherapy) but recent testing showed my TMB jumped up from 1 to 10.5, which is an indication that CDK4,6i may have stopped working, so if I have to drop Verzenio anyway, well there is no point staying with Fulvestrant. The test showed 0.2% ESR1, which is so tiny that I wonder if its better to stay on Fulvestrant and let its prevalence rise, ie would that make it more endocrine-sensitive? I doubt she knows, but staying on Fulvestrant alone is just too dangerous anyway. And we don't have other options for endocrine backbones, outside of trials.
I haven't read that Elascestrant gives much hair and nail thinning, whaddya think about that?
PS Well, bone-only people wouldn't see shrinking regardless, but stable is great. Sounds like you have to make it past the first 2-3 months to get a sense of whether it will work, because there are a lot of people who crash at the start due to endocrine-resistant cancers…
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PS You would think that those with high percentage ESR1 mutations would do the best, but I have read there are other categories who did relatively well, those who failed Fulvestrant specifically, for example, and some have wondered if the FDA won't in the end open up Elascestrant to all subtypes, I imagine it depends on how Elascestrant looks relative to the other SERDs when the data are all collected.
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Hello all. Took my first elacestrant pill yesterday, after nearly three months of no cancer treatment at all. Amazing how long it took to get this last drug going. Five weeks. My oncologist didn't seem to have much hope for it, but that wasn't the problem. The problem was turnover in my cancer center and they fumbled the ball with the paperwork, which stalled three times. Gave me the impression they couldn't keep track of things there and were relying on me to call and remind them.
Yesterday was also my nine year cancerversary. If I had any regrets, I would say - should have travelled in the beginning when I felt well and we had no pandemic. Hindsight is 20/20.
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cure-ious,
I don't remember anyone from the FB group reporting hair or nail thinning. Skin rash has been reported. I start week 4 tomorrow and have not noticed any hair/nail changes. I really haven't had any side effects so far. One important thing is to take the pill with a large, high fat meal (800-1000cal) followed by plenty of water. Those who skip or skimp on these guidelines seem to be the ones who get into trouble with gastric reflux and/or nausea/vomiting. The kind of fat most mentioned includes nut butters, peanut butter, avocado, ice cream, Greek yogurt. Some women mention that the pill, which is big, goes down hard and ends up feeling like a lump, which then causes reflux and heart burn. So some women take antacids or acid reducers. I take mine buried in mashed up avocado (I buy avocado mini cups) and that has worked well for me. I've learned from this FB group, but I find the many different discussions hard to follow. I prefer BCO.
ninetwelve,
I often find I have to do my own case management and I think it's more than just advocating for myself. My impression is no one really seems to be responsible for keeping track of the many details of my care. When Orserdu was ordered, I had to call to ask what the lab frequency would be and the first answer I got was, "we don't know - it a new drug". Thankfully, that detail did get clarified pretty quickly. But getting the drug filled by the designated specialty pharmacy also took several phone calls on my part. It would have eventually gotten done, but with frustrating delays.
Hoping the best for both of you.
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To All,
Two commenters on the Facebook Orserdu site have recently said their MOs told them ESR1 mutation percentage does not matter in terms of treatment efficacy and it was not followed in the trials.
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weninwi thanks for sharing the info
ninetwelve, I am glad you received your med, and I hop this break from treatment has helped you recover from the side effects. I thought once a drug ie. Elacestrant has been approved by fda there wouldn't be any problem with getting a prescription and the medication. have you been waiting for the prescription for the entire 3 months, or is it recommended to be off med before starting Elacestrant? my MO has not instructed me to stop my current treatment, and I don't know if I should be off my meds for some time before starting Elacestrant? probably she wants to see the 3-month scan report but the liquid biopsy has already shown the mutation.
does everyone who started Elacestrant have mutations other than ESR1?
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snow-drop - I had a bad reaction to a chemo, which was responsible for two of the months of treatment pause. The other five weeks or so, I was trying to get approval from my insurance, and then financial aid for the $3000 co-pay for Orserdu. (Yes, that works out to one hundred dollars per pill.) I finally got the aid my orserdu for the rest of this year will be free.
I have lots of other mutations, including the FGFR-1, PIK3CA, PTEN, and TP53.
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Update:
Onco360 delivers the Orserdu via Fed Ex and requires a signature. Fed Ex came today - I was inside the house, but the driver did not knock and nor ring the door bell. As he was leaving with the package, my husband thankfully arrived home from an errand and signed. G-r-r-r. If my husband had not saved the day, I would have had to track down the package and go pick it up and sign. Next time I'll put a note on the door - "I'm home, please knock loudly and ring door bell". Next week I have first labs and appt with MO since starting the Orserdu. Still no side effects except maybe a little fatigue. Wish this discussion board was more active. The private Facebook group has 312 members now.
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wondering if anyone is combining Elacestrant with another targeted therapy? I understand there are trials underway testing it with the standard Cdk inhibitors. Is anyone on that trial or can Oncologists prescribe a combination? I am currently on Xeloda but markers continue to rise so I am guessing my next line is imminent.
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