Abemaciclib Verzenio for Stage IV
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50sgirl, welcome. I'm starting my 5th week of Verzenio and so far only a couple days of diarrhea, but Imodium quickly took care of it. Otherwise, I'm feeling quite good. I've noticed thinning hair though, that's my biggie SE. Hope this tx treats you well and works well for you.
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So, my appt today was with another of MO's PAs. We discussed possible next steps, but she said although I did have some progression, they think I haven't been on this treatment long enough to make a difference since I was off tx for a while. So, we're gonna give it another month or two unless my TMs skyrocket or liver enzymes go crazy. We'll rescan and then reaccess. Sounds reasonable.
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wishing you luck!! Could beit just needs more time. I know they typically scan every 12 weeks (as they do with me), but what is typical? and for some people the cancer may be too aggressive.
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Bliss, My TMs jumped in the first month, then declined regularly since then. My 3 month scan showed marked improvement.
Hope, The original plan for me was to scan every 3 months, but my TMs seem to be sensitive (I know they aren't for everyone), so if this month's scan is good, we may go longer before the next one - using TMs to monitor status. I think that's unusual, but I'm comfortable with it...as long as this next scan is unequivocally good.
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To Sadieservant - sorry that Verzenio treatment has come to an end for you. I appreciate all the messages you have sent to encourage us through this treatment. I am hoping the next care treatment for you will be effective in treating the cancer and have manageable side effects. Best wishes.
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yes! my TMs matched the shrinkage and then stability from the treatment. Was doing so well that they were going to start pushing my scans out...4 months and then maybe longer. Right after that decision my TMs started to rise. We’ll know what that means with next scan in March....back to 3 months!!! Hope you continue to do well!!!
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Sadieservant- I was wondering about your treatment, after Ibrance-AI you went onto Faslodex for quite awhile as monotherapy, and then later added on Verzenio? What was the strategy there and what change happened to make you decide to add Verzeio? Thanks!
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Hi Cure-ious,
It was purely strategic timing on my end. The PFS for Faslodex is about 8 months so I started to get a bit more watchful after a a year and a half. There was some suspicious skin stuff and an uptick in bone pain but nothing super ominous so we continued. My MO and I had talked about adding a CDK inhibitor but he wouldn’t consider Ibrance again. Verzenio was my preferred but it wasn’t available in Canada. It was finally approved in summer 2019 but difficult to get. They were very narrow in their consideration of use, would only support it as a second line and while on paper it was approved as a monotherapy it was highly unlikely that was an option any time soon. I was pretty sure that if I didn’t get it now it would be impossible later. I was turned down the first time. Tried again and this time successful but insurance denied me. Fortunately MO was able to get it through compassionate access with LillyPlus. I do believe I made the right decision. I had hoped I could squeeze more time out of it but...
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Sadie, Thanks, you obviously did really well in terms of the time you got out of these treatments, and I am wondering between keeping on with Ibrance or whether its time to switch it up to Verzenio (still waiting on Foundation One, the slowest blood test ever). I could keep on Ibrance change to Faslodex, scan and then if its not working try switching the Verzenio, or just switch both- its crazy we have no biomarkers to go on as to whether or not the CDKi is working (or indeed whether it ever worked in the first place, in principle we take this drug only because on average, most people respond). Hope Xeloda works well for you!!!
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Cure-ious,
I can’t recall if you have progression. Is this why you are considering a change? I couldn’t tolerate Ibrance - my hemoglobin tanked which is why my MO took it off the table. He’s pretty convinced I am now resistant to hormone treatments so it will be chemo from here on out unless we get the genie back in the bottle and I convince him to try A/A or Tamoxifen.
Really hoping for good results from Xeloda as I burned through quite a few options during my first year. I do worry about efficacy with chemo however as my cancer has been a bit more on the slow, plodding side. It may have picked up the pace though as scans in October were clear.
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Sadie, Indeed I have progression, so we are waiting on Foundation One to see if we can get a clue about what is behind it, and especially to see if the cancer developed an ESR1 mutation, which would mean that I have to go on a clinical trial to try to clear that away. You definitely can and should cycle back to endocrine therapy after chemo works, hopefully for a long time, but I think by then there will be strong SERDs (oral and stronger than faslodexm and decidedly stronger than tamoxifen or AA) that can be combined with Verzenio- in the preliminary trials some people are getting another year or two on those even after 5-6 rounds of prior therapies that included CDK4,6i and Faslodex. And if not a SERD then the Androgen Receptor booster drugs that can also shut down estrogen signaling and work on endocrine-resistant cells. And by then, there should be some immunotherapy combination trials that are worth joining! Hang in there- you just started Xeloda, how is that going?!
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Thanks Cure-ious,
You always give hope and a lot to think about. To be honest, I’m feeling the weight of mortality at the moment but am starting to get my fighting spirit back.
Xeloda is being kind to me and I’m even trying to convince myself that the pain is less. Let’s go with that!
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I have this same problem. It is rough! All over my legs and torso. Ouch!
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Hi all, I've been on verzenio and faslodex for about 9 months now and I'm starting to notice some pretty significant hair loss. I only just gave up wearing a wig after losing all my hair to AC chemo and I am not excited about the prospect of going back to it. I know it's so small in the scheme of things - and this topic has probably been talked about before - but has anyone experienced hair loss on verzenio? Have you found it tapers off or keeps increasing? Anything that others have found helps to combat it? (I know that's wishful thinking but I can't give it up just yet...)
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Starting verzenio tomorrow. Already taking Arrimidex- 1st month. No chemo. Just hormone a d targeted therapy. First scans in 3 months m
Please send good thoughts and prayers along with suggestions on dealing wiry side effects
Chatham Lady
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I wish you much luck! I have been on a CDK4/6 inhibitor for two years now. I started with IBRANCE but my ANC levels were so low that I needed to switch over to VERZENIO after trying for 6-7 months. For me the major issue has been diarrhea. I had that early on, seemed to get it under some control but only with max dose of Imodium and lomotil, but then lost all control, lost a lot of weight, after about 6 months. This was also right around the time I had to add Faslodex and Xgeva because of the appearance of a bone met. Not sure if that is what broke the camels back. I had to switch from the 150 mg two times per day down to 100 mg two times per day. Felt like a human being again at the 100 mg dose. Still had some issues, but using Metamucil 2x/day seemed to take care of them. I still use the Metamucil occasionally and also pop an Imodium now and again. But nothing like before. I have a very varied diet although I am cautious on eating things that are too rich and too spicy. I have had some fatigue, but not like others. I am not working, so I’m able to sleep for a long time at night (9-10 h) which seems to get me the rest that I need. Some people have a lot greater issue with fatigue. My ANC levels never went back to the normal of 2.0, but they have been pretty steady at 1.5 and that’s enough to keep me on VERZENIO. A number of people have reported hair loss. I did go through a period where I lost some hair and my hair got exceptionally dry and bone straight. The hair loss seem to have stopped for me and lots of conditioner and good cuts seem to have helped get my hair back in some shape.
Unfortunately, my tumor markers are starting to rise and so I’m not sure what that may mean for me remaining on VERZENIO. I’ve got scans in early March and we’ll see what happens the. I was diagnosed with liver Mets as the first site of metastases. You can see more of my profile, which I leave pretty extensive.
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Chatham Lady,
Welcome. I'm sure this isn't where you really want to be, but you will find a lot of support and information here. You haven't shared your profile/history, yet. Were you diagnosed de novo? If so, be sure to check out this thread De novo Stage IV.
I started on Verzenion + Anastrozole (generic for Arimidex) in July as my first line tx. It was a rough start: lots of fatigue, which improved when I retired from my very stressful job, but it's still there; diarrhea starting after about a week, controlled with immodium and metamucil (big help); food aversion, but no nausea; some hair thinning; joint pain - especially my hands and feet and sometimes hips, but it's better after moving around a bit. I lost about 20 lbs the first month, or two, but then leveled off. I'm not sure if the hair thinning has leveled off, yet - and I blame going from HRT to AI for part of that. I feel like my ponytail is about half as big as it used to be, but I'm probably overestimating, because my hair still looks okay. My skin, scalp, and hair dried out, but moisturizing (love the Nivea in-shower lotion) and a good conditioner help. I usually only wash my hair every 2-3 days now (it used to a must be every day!). I also use argan oil on my hair and rub it into any super dry places on my scalp. I understand the joint pain is a pretty common SE of the AI, so may not be from the Verzenio.
Oh, and my TMs spiked the first month after starting treatment, dropped only a little the next month (that concerned my MO), but then made big drops on the third month and subsequent tests. TMs are not good indicators for everyone, but my MO thinks they are for me, so far. I guess we'll find out, for sure, after the next scan.
There are a lot of ladies that needed a dose reduction - and still had successful treatment - because their SEs were extreme; I'm sure they will chip in with their stories, which could be helpful to you. Mine leveled off, or improved, after a few months and I am still at the full dose (150mg, twice a day, pluse the AI). My first follow up scans were three months after and showed marked improvement. My next scans are next week, and I'm hoping for more good news.
Good luck with your treatment and be sure to come back and let us know how you're doing.
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mshar ,,, i. Any comment too much on Hair loss. I had radiation to my skull so I feel o lost some due to that couple months ago. You can’t tell too much but my hair is very dry
Chatham lady,, welcome and hope verzenio treats you good.
SeeQ,, Good luck with scans.
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ChathamLady, welcome to the thread.
This is the start of my 9th week on Verzenio. So far it's treated me well. No nausea and just a couple bouts of diarrhea, but nothing Imodium or Metamucil didn't help. I noticed my hair thinning and that's my biggest SE. It's very dry, so I only wash it every few days and need to condition well, but the good news is the thinning seems to have slowed the last couple days.
Sending you good thoughts that this treatment will be good to you.
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Thought I would chime in even though I am not on this drug as of two a week ago. Hair loss? Not extreme but definite thinning (of course radiation to skull mets wiped out the hair on my nape with no signs of it returning yet). Diarrhea was never an enormous issue for me but I did experience it, initially once a week or so, with severe cramping leading to watery diarrhea. I also had symptoms ramp up at about the eight month mark with the diarrhea significantly increasing in frequency to several times per week. A dose reduction took care of that. The fatigue was definitely an issue. I've been battling fatigue for over a year and remarkably, after only one week off the drug, I have seen a significant improvement despite issues with my liver and a move to oral chemo. Interesting.
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What are women's experiences with dose reduction and continued successful treatment? My wife is on 150mg 2x daily and is experiencing so much fatigue. Anyone know of any research on this subject?
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Found this on Inspire:
April 4, 2019 at 4:45 pmDear Waldbet:
I can provide you with some reassuring evidence on this issue:
An exposure–response analysis was recently conducted using data from PALOMA-2 to assess the effect of changes in palbociclib (Ibrance) exposure (due to dose modification / reduction) on progression-free survival (PFS) in patients [Zheng 2017]. What they found was that the median PFS was similar in each dose level group, so duration of progression-free survival (PFS) was NOT associated with palbociclib exposure. These results suggest that patients who had different exposure levels to palbociclib due to dose reductions or interruptions still benefited comparably to those who didn't, and that the dose reduction algorithm implemented in PALOMA-2 (from 125 mg, down to 100 mg, down to 75 mg as needed) effectively managed palbociclib toxicity without significantly affecting it effectiveness or treatment outcome (see also: [McShane 2018].
These findings from the PALOMA-2 trial were then confirmed in PALOMA-3 where dose reduction (down to 75 mg) did not impact efficacy or survival outcome [Verma 2016]. The safety analysis from the PALOMA-3 trial showed no difference in PFS among patients who had dose reductions or delays, usually secondary to neutropenia.
Finally, another retrospective study analyze the impact of dose delays and reductions on toxicity and progression free survival (PFS) in patients receiving palbociclib (Ibrance) [Clifton 2017].
CLINICAL LESSONS LEARNED:
(1) Survival outcome (PFS) is NOT negatively affected in patients who required dose reductions and delays, whether early in their cycles, late in their cycles, or throughout the cycles.
(2) Patients who are experiencing adverse side effects that are appreciably compromising their quality of life (QoL) SHOULD NOT HESITATE to request dose reductions or delays, since this will have no significant negative effect on their survival outcomes.
(3) Patients who DO undergo dose reductions or delays tend to have significantly higher health-related QoL and experience significantly fewer adverse side effects.
BOTTOM LINE: DOSE REDUCTIONS AND/OR DELAYS ON PALBOCICLIB (IBRANCE) DO NOT COMPROMISE CLINICAL SURVIVAL OUTCOMES.
LOWER THRESHOLD: STRUGGLEBUSTED and JOSIEGIRL:
Unlike reduce doses at 100 mg and at 75 mg which make no material difference to efficacy and survival outcome, we just don't have dose-outcome study data for reduction down to 50 mg. The official FDA dose guidance indicates "If further dose reduction below 75 mg/day is required, discontinue". This does NOT mean that dosing at the 50 mg level is without clinical benefit, ONLY that we LACK any supporting data to tell us one way or the other.
However, I will report some of my own impressions and experiences.
First, we have suspected that with the current three-week on and one week off schedule, a significant number of patients develop grade 3 or higher degree of neutropenia and require dose reduction and sometimes discontinuation, BUT more importantly with the one week break with the standard 3 weeks on and 1 week off dosing schedule, the fear - including my own - is that this could potentially lead to recovery of Rb phosphorylation (what's being suppressed by palbociclib (Ibrance) during the off week, which would allow for progression in the so-called "vacation period" on one week off.
This is the motivation for colleagues at the Washington University School of Medicine (WUSM) conducting (under Cynthia Ma as principal investigator) a clinical trial (NCT03007979) testing a novel dosing schedule of a 5 days on and 2 days off (5-on/2-off continuous) schedule each week - every week with no weeks off drug. It turns out that if you do that the cumulative doses each 28-day cycle is just about the same with this (5-on/2-off continuous) schedule compared to conventional dosing, BUT now the bone marrow is not assaulted with the drug continuously for 21 uninterrupted days, now getting frequent breaks from therapy. What the investigators hypothesize is that the 5-on/2-off continuous schedule is more tolerable AND with less frequent high grade neutropenia and so with less need for dose interruption/reduction. A BONUS: this schedule also provides for a more continuous drug delivery since it abolished the week's break in therapy, so the speculation is that it could ultimately prove to be more efficacious AND more tolerable and avoid drug reductions and delays.
AND although we don't yet know the final trial outcome - the trial began June 2017 - it is coming up to a FINAL completion date of February 2021, but it has a PRIMARY completion date of March 2019, so I am expecting some early results to be reported (formally or informally) in the next couple of month or so hopefully. But to me the novel schedule makes excellent "molecular" sense and similar dosing schemes with other agents that Larry Norton at MSK pioneered have always been successful, so the promise is good.
SUGGESTION:
Given that we have no data on the efficacy of a reduction down to 50 mg, one experimental option your oncologists might want to entertain is the WUSM trial's 5 days on and 2 days off (5-on/2-off continuous) schedule with the high likelihood of greater tolerability since the bone marrow takes a hit only for 5 - not 21 - days, before getting a vacation of 2 days to recover. Currently the trial protocol starts at 125 mg for 5 days a week, then 2 days off, repeating the cycle weekly, but a fallback position could still be 100 mg using the sane schedule. Me, I suspect that that reduction would not be necessary, but it's available under duress.
REFERENCES
[Clifton 2017] Clifton KK, Kimmel J, Yi M, Chad B, Litton J, Debu T, Meghan K. The impact of dose delays and reductions on toxicity and progression free survival (PFS) in patients receiving palbociclib [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-11-03. Also: SABCS 2017 Abstract: 1261
[McShane 2018) McShane TM, Wolfe TA, Ryan JC. Updates on managing advanced breast cancer with palbociclib combination therapy. Ther Adv Med Oncol. 2018; 10:1758835918793849.
[Verma 2016] Verma S, Bartlett CH, Schnell P, et al. Palbociclib in combination with fulvestrant in women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer: detailed safety analysis from a multicenter, randomized, placebo-controlled, phase III study (PALOMA-3). Oncologist. 2016; 21:1165-75.
[Zheng 2017] Zheng J, Yu Y, Durairaj C, et al. Palbociclib exposure-response analyses in the treatment of hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2–) advanced breast cancer (ABC). 2017; Abstract.
Constantine Kaniklidis
Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)
Oncology Reviewer, Current Oncology
Member, European Association for Cancer Research (EACR)
Society for Integrative Oncology (SIO)
International Cardioncology Society, North America (ICOSNA)Edited April 4, 2019
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A post on Inspire:
Your dose reduction of abemaciclib (Verzenio) should be unproblematic, as it's been studied and sanctioned as effective (First dose reduction to 100 mg, Second dose reduction: 50 mg BID.
That's been decisively confirmed in the Final PFS Analysis [Johnston 2019] of the MONARCH-3 clinical trial published January of this year, where it was found that survival (PFS) was not significantly different at 100 mg and 50 mg from the 150 mg standard, so you have no cause for concern.
Best fortune with the scans today (and remember, median TTR (time to response) is no less than 4 cycles (3.7 months), and a sizable proportion of patients needed exposure out to 5 - 7 months for clinical benefit).
REFERENCE
[Johnston 2019] Johnston S, Martin M, Di Leo A, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer. 2019; 5:5.
Constantine Kaniklidis
Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)
Oncology Reviewer, Current Oncology
Member, European Association for Cancer Research (EACR)
Society for Integrative Oncology (SIO)
International Cardioncology Society, North America (ICOSNA)0 -
Hi Husband,
I think Constantine is spot on and really appreciate the confirmation.While I have now progressed, I am confident that this is due to resistance and not dose reductions. Verzenio is a challenging drug in many ways so modifying the dose is imperative IMO in order to stay the course.
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That's interesting about the median time to response being 3.7 months.
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Husband 11 - Part of the reason that they won't do the first scan until 3 months.
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I find it interesting about the median time to response being 3.7 months, too. Shows I got way ahead of myself thinking this treatment isn't working. Somewhere, maybe here I think, I posted that I've been on this treatment going on 9 weeks when in fact I'm only starting my 6th week tomorrow. No wonder MO wants me to stay the course. My PET showed progression, but I'd been off treatment for 6 weeks prior to starting Verzenio. My last PET was in September, so they're looking at this latest one as my baseline and will rescan in 3 mos.
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praying bliss that it’s doing it’s job!!! I wondered about your early scan. Hoping at 3 months you are at least stable and the the verzenio thenstarts to shrink these bastards!!!!
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My wife's tumor markers continued to rise after her 1st 6 weeks of treatment with verzenio, but from graphing it, it wasn't anything close to what I would have predicted. That suggested the treatment period might have slowed the increase, or reversed some of what occurred leading up to it. We saw a reversal on the 2nd 6 week period, and an even larger decease on her third. I might have the time frame slightly wrong, but she gets her blood tested roughly every 6 weeks. Hard to say if its the verzenio, the switch to exemestane, or both.
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I hope the slowdown is due to treatment and hard to say exactly which one, likely both since they are acting together if she is sensitive to AIs. Don't get too hung up on TMs. They are important for the whole clinical picture but they don't tell a story on their own. Some MOs won't even have TMs tested because they can cause great anxiety for the patient and they are not ever used on their own to make treatment decisions. I had an increase in my TMs when I started treatment with cdk 4/6 inhibitor and they declined with time (months) and then leveled out in the normal range as I attained "stable disease". They held stable for many months and have started to increase again, although my last scan in December still indicated stable disease. Will see what the March scans can tell us. Preparing myself, but since they are not skyrocketing, I am not going into any panic and neither are my MOs. I have been on a cdk4/6 inhibitor for 2 years this March. I am praying for longer time on it, since of course I am now tolerating the treatments very well, but the scans will tell.
Good luck with this treatment!!!....when are your wife's first scans?
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