IBrance alternative dosing schedule : (5 on 2 off) another trial in the works

[Dragonfly2]

To those who are following the news about the alternative dosing schedule (5 days on and 2 days off) for IBrance : not only is this schedule effective for those who have been suffering from neutropenia after 21 day exposure to IBrance, there is a other trial phase two ending on December 2022 that is studying whether this type of dosing schedule is actually better for patients without neutropenia for other reasons.

clinicaltrials.gov/ct2/show...

in the summary: The investigators propose to conduct a study to test an alternative dosing schedule of palbociclib. 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. This potentially compromises the efficacy of the drug. In addition, as the half-life of palbociclib is 27 hours, 1 week break with the standard 3 weeks on and 1 week off dosing schedule could potentially lead to recovery of Rb phosphorylation during the off week. Hence, the investigators propose a 5 days on and 2 days off schedule each week without any weeks off drug. Although the cumulative doses each 28-day cycle is roughly the same with this schedule compared to conventional dosing, the bone marrow is not exposed to the drug continuously for 21 days and rather gets frequent breaks from therapy. The investigators hypothesize that the 5 days on and 2 days off schedule is more tolerable with less frequent high grade neutropenia and dose interruption/reduction. In addition, this schedule also provides for a more continuous drug delivery to the patient since there is not a week's break in therapy, which could ultimately prove to be more efficacious.

The key words are : Rb phosphorylation . This has to do with how tumor suppression is effected by IBrance .

Ultimately this study is poised to show that taking the IBrance continuously with only 2 days off actually is more protective for the patient and keeps the tumor cells from replicating.

Personally, this schedule has always made sense to me and I was really happy to find out this past year that the original study found it to be as effective as the 21 day cycle while preventing neutropenia. Now, this this will hopefully show that the 5/2 schedule actually makes the med ss even more effective.

Fingers crossed ladies…🥰🙏

[OneLump22]

🤞 Dragonfly. I had an interesting experience today with my Ibrance. My Onc has me on 125mg 21: 7 & normally, during the 3 weeks I barely eat 'cause I have no appetite. But this afternoon I was craving chicken noodle soup & hamburger bun with lime flavored mayo. Dinner was a Michellena's beef teriyaki & noodles & then I found myself sitting at my stove in my rollator walker making great northern bean soup with salted pork pieces, French onion dip powder mixed in, & tomorrow I'm making corn bread muffins (maybe). Also having sudden craving for red beans & rice (red kidney beans soaking as I'm writing). This is wierd for me after nearly a year of, I guess, what amounts to intermittent fasting.

[Dragonfly2 in reply to OneLump22]

glad you’re eating again! Though I know that many MBC patients actually gain weight easily because of the meds…good nutrition is key…your choices seem to suggest you’re craving what you’ve been missing. Bon apetit!

[BritSammy]

thank for sharing this very interesting research Dragonfly 2. I am currently on the 21 day cycle of 100mg Ibrance and regularly have neutrophils below 1 at the end of the cycle. I am also always low in potassium. I mentioned the 5 day 2 day off to my consultants (in the UK) and they said no this is not effective do not follow this. I am due my 6 monthly scan tomorrow so we will see how effective the medication has been doing for me. Definitely have scan anxiety.

[mariootsi in reply to BritSammy]

I wish you well and peace on your scan! Scanxiety is just awful!

[Godbeforme in reply to mariootsi]

so nice to see you! I can never remember anyone's real name DUH! anyway, I am back on the IBrance and reading up on the five two dosing schedule, I did get netropenia last time I took it. I started it again because it worked and it didn't quit me, I quit taking it when I had chest pains a few days in a row and it scared me. I should have just stopped for a while ... but oh I didn't come in here to babble, just to speak to you and say how nice it is to see you. I hardly see any of the ladies who were here when I started coming in, so sad, this disease ... I don't know if it will kill me first or drive me crazy LOL ... If I didn't have Jesus ... I definitely would not survive, He keeps me steady. love to you and God bless you and heal us all in Jesus name, amen! <3

[mariootsi in reply to Godbeforme]

Amen! So good to have u here! I'm Marianne. Like you, I think it's going to drive me crazy too! Lol

[Godbeforme in reply to mariootsi]

I was thinking maybe Marie, because of your nickname, close but no cigar! LOL Have a blessed day, Marianne! <3

[love2golfwell]

Thank you for sharing this information. I have been doing the regular Ibrance protocol at 125 mg for the 3 weeks on, 1 week off for the past 2 years. I have never had really low WBC or neutrophils. I have been doing well on this, but I would definitely be willing to try the 5/2 schedule if this study proves successful. I think I would even want to try this schedule if I had some progression before I would agree to switch to another treatment as I think a more consistent dosing of the Ibrance would be helpful. Good luck with your protocol. Please keep us posted if you find out any more information about this study.

[mariootsi in reply to love2golfwell]

I spoke to the specialty pharmacist about the 5 / 2 dosing. He never heard of it. It figures! I don't think they keep up with the alternative stuff. Just the set standards.

[mariootsi]

Yes. Fingers crossed! I'm going to talk to my onc about this at my appointment in December.

[bracelets1]

Thank you for sharing this information. I don't have any problems with my current 3 weeks on 1 week off, but I always find these alternative schedules very interesting and keep them in my mind just in case......Blessings!!

[Half-Full]

Interesting and encouraging, but not exactly surprising. Seems like the protocol they use on all these drugs to derive recommended dosing is somewhat flawed. The focus in these prior trials and studies seems to be more on “maximum dose tolerated” as opposed to “minimum dose efficacy”. Hopefully this is changing. A new approved iBrance dosing protocol might also reduce the risk of other complications such as pneumonitis which I encourage everyone who’s on CDK 4/6 inhibitors to please research and be aware of those symptoms. Thanks for posting. I hope this comes to fruition and helps with quality of life considerations, if not improve its effectiveness.

[25047]

thank you for this info, as a Nurse, this 5/2 study makes so much more sense to me physiologically❤️

[hurricaneheather]

this mind-body was perplexed with the 21-7 treatment cycle. after trying it, i requested a different treatment cycle, 14-14. now, a different one, which the mind body has been receiving for years. it is one i requested, based on drug research and the half life of Ibrance. thankful to remain NEAD, through all the cycles. and, the onc wants me to stay on this treatment cycle!

[mariootsi in reply to hurricaneheather]

Never heard of 14/14 dosing

[Dragonfly2 in reply to mariootsi]

I haven’t really either! Just shows that there are people who can’t tolerate the 21/7 schedule snd must try other things. My experience with the 5/2 has been very positive. 😅🥰

[hurricaneheather in reply to Dragonfly2]

it makes the heart happy to know the 5/2 has been very positive for you. even the lowest dose was too much medication for this mind-body. thus, the change of dosage and schedules. after researching Ibrance, i approached the onc.

[hurricaneheather in reply to mariootsi]

it was initiated by me, after researching Ibrance. the onc approved it.

[Hazelgreen]

That is good news! My oncologist is not supportive but, on my own, I've been trying the 5 days 0n /2 days Off with ribociclib. After 6 weeks on this schedule, and bloodwork every two weeks, it appears that my neutrophils stay reasonably level, and I've not needed the extra week off I did before. Since the half-life of ribociclib is even longer (32 hours) than Ibrance, this all may make sense so I hope this schedule is also studied with the other CDK 4/6 inhibitors.

On a related theme of mine, I am still looking for a study that tells us why some cancer patients do so well on letrozole alone. Clearly, some women in the control groups are surviving many years, and we need to know how they differ from those who need a CDK inhibitor.

P.S. I checked out the link Dragonfly provided, it looks like 55 participants are involved in a single group with the same measures being taken as in the original study...

[Dragonfly2 in reply to Hazelgreen]

HazelGreen! You’re a brave soul! I’m glad you are seeing an improvement in your health…and yes, it does make sense. Hope your health continues to be good and you enjoy this respite. Yes, some people do well on just the aromatase inhibitors…and I remember reading early trials questioning the actual efficacy of IBrance…if it really was all that it’s cracked up to be. I hope that this alternative dosing is helpful to many, many more !😍

[Granny333]

I hope so , I am going to ask my Dr about it next visit

[Dragonfly2 in reply to Granny333]

Great! Do make sure you share the links to the trials …

This was the original trial to show that the alternative dosing was effective to prevent neutropenia: pubmed.ncbi.nlm.nih.gov/353...

This is the trial about this alternative schedule finishing in December to prove that it may be even more effective for tumor suppression : clinicaltrials.gov/ct2/show...

My onc did not want to prescribe this alternative dosing until I showed her the trials…your Onc may have reasons to be reluctant in your case but it won’t hurt to provide evidence. Toooften when they’re in th trenches they don’t stay up to date on recent research, 🙏😇

[Godbeforme in reply to Dragonfly2]

I'm so glad you posted this! I am just on day 8 of my first ibrance cycle and watching for the study. I almost did the 5/2 right off the bat, but then decided since the cancer has spread and I've been off of it for so long, I had best get the 21 days in for starters and then I will have the new study to refer the onc to. I know we can do what we want but it is nice to have a good and honest relationship with the doctor and no secrets, however, after hearing you are doing so well with it, and when I read the new study that confirms this, I will definitely do the 5/2 because the oncologist isn't the one who has to suffer with the neutrophenia, is he/she? we are the ones who have to live with our choices after all is said and done. Thanks again for posting the link for the study that wraps up 12/31/22! God bless you and family and Merry Christmas! <3

[Laskia]

I'm due to see my oncologist in December, so I'll go armed with the studies and see what happens. If they wont budge on the dosing schedule without a good reason , I may consider doing my own clinical trial and switching schedules.

[Dragonfly2 in reply to Laskia]

hi! I had to talk to my onc several times..but providing her with the trials seemed to do the trick. My biggest argument was how could the medicine work if I was off it for two weeks at a time trying to recover from low neutrophils. The ONc definitely didn’t want me to drop down to the 75mg…so ultimately the results of the trials registered…taking the meds regularly meant that the meds had a chance to work.

I know that doctors are reluctant to do anything that may be considered unethical…they don’t want to be sued. I suspect this new protocol is becoming more frequently applied. Best of luck…ultimately you’re responsible for you😁

[Godbeforme]

Good morning and happy 2023 to you! Do you know if the results are out yet for the study that finished on 12/31/22? I am a bit anxious for the results because I just completed my first cycle and really want to try the 5/2 as I've had a nose bleed for 5 days and I never get those, for one reason I am in a hurry to know the results of the 2nd study. Thanks and God bless you and heal us all in Jesus name, amen! <3

[Dragonfly2 in reply to Godbeforme]

Hello! No I haven't heard anything...if the trials ended successfully they have to first study the results. I went ahead with the new doing because it works for me ...these past 5 months have been among the best, worry free months Ive had on this drug. I haven't had to take a week off and I feel well. Do pursue this if you feel there may be a benefit for you...but realize that you are in the beginning cycle of your treatment and there are lots of things that may change or improve. It took me two years to make the switch and for me it has resolved the issues I was having with fatigue, depression and neutropenia. If you can, continue to search for new trials regarding this: look for alternative dosing for Ibrance. Thank you and all my best!

[Godbeforme in reply to Dragonfly2]

the thing is, my markers went UP instead of down but onc said it can take months to bring them down. thanks for the advice, I think I'm going 5/2 coz my bp has been high and I had a nosebleed the last 7 days with it finally letting up today after 5 days off the meds (my week off) ... sorry to rattle on, I have a lot of stuff going on today and I'm a wreck! <3 thank you!

[Danie-in-Montreal]

Thank you soooo much for posting this! I plan on bringing it up with my oncologist. <3