Two interesting articles related to palbociclib

[Evbr]

I’d like to contribute with people taking palbociclib. The first article below (Google the titles please) suggest possible increase in PFS and the second (that diectly can affect my wife’s treatment) will be presented this week in a conference.

Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients

Overexpressed cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors

I’ll post sometime later (long post) an update on my wife’s treatment, but unfortunately she had to stop palbociclib after 29 months and is now on Afinitor.

Regards

Eduardo

[Bettybuckets]

Thanks for making us aware. I can’t wait to read others take on this as it sounds promising for some of us worried about progressing on Ibrance

[Hidden]

Hi Evbr, Thank you for sharing this valuable info...

I feel ill-qualified to respond, since I lack the education/erudition of the others, but -- as is often the case (!) -- I'll not let that hold me back!

I looked a bit into PPIs and see that common drugs, such a Prilosec (sp?), are included. This concerned me because I *think* this is often used to treat something as common as "acid stomach". Which I think is pretty common in people, in general, and especially in women (?), maybe especially of a certain age? I think lifestyle factors might also matter...weight, body type, stress, etc. So I would not be surprised if those of us dealing with this offing disease are more likely than most to be taking PPIs?

This study reinforces my belief that we need to focus on "Job 1", fighting cancer. Any side-effects (e.g. nausea), other "minor" issues, etc., should be set aside/ignored. Muck with your system as little as possible, let the cancer drugs do their job. Mind you, I exclude from this statement well-researched/considered drugs/supplements/protocols that might help fight the cancer. Job 1.

It's so disheartening to read that something as simple and common as a PPI can potentially sabotage the life-extending treatments that we benefit from. **If I understand what I read correctly** (never a good bet!).

Take care,

Lynn

[Hazelgreen in reply to Hidden]

It seems to me, Lynn, that, as usual, you understood the conclusion of Eduardo's article perfectly. I like your idea that our Job 1 is fighting cancer, and, beyond that, we should avoid messing with our systems!

Cheers,

Cindy

[Hazelgreen]

Thanks, Eduardo for these interesting articles. I noted that the 2021 take-home message for clinicians from the first article (published in 2021) was as follows:

"This study of 112 patients with ER+/HER2− metastatic breast cancer was designed to evaluate the effect of coadministration of PPIs and palbociclib on progression-free survival. Of these patients, 56 were taking concomitant PPI therapy for cancer drug–related gastrointestinal symptoms, and 56 were not; 71 were estrogen-sensitive and 41 were endocrine-resistant. Patients receiving concomitant PPI therapy had significantly shorter progression-free survival compared with those not receiving PPIs (14.0 vs 37.9 months). Progression-free survival was significantly longer without concomitant PPI therapy among patients with estrogen-sensitive disease compared with those taking PPIs or in patients with estrogen-resistant disease with or without PPI therapy."

It seems clear to me that those of us with endocrine-sensitive disease would be well advised to avoid PPI therapy so thank you, Eduardo, for providing us with this information.

The second reference you provided led to several relevant articles that may offer hope for those for whom palbociclib no longer works. It seemed to me that these alternative approaches may still be in the development stage but I didn't really spend sufficient time on them.

I applaud your deep concern for your wife's welfare. I do hope she does well on Afinitor.

Warmest of wishes for you both,

Cindy

[Evbr in reply to Hazelgreen]

Thank you Cindy. My wife started taking dexilant this year, After pantoprazol. This may have worsened her PFS on ibrance.

The question are: do ibrance can resume its job efficiently on her if she leaves those PPIs? Did she created resistance? Can everolimus revert this possible resistance after some time?

I hope everolimus works but would like to think a possible return to ibrance after some time.

Regards

Eduardo

[Hazelgreen]

Thanks, Sandra, for these three references which seem closely related to the research articles Eduardo provided. I do agree with you that the articles give "hope for the future of these type drugs". Unfortunately, it is not clear when new drugs to overcome resistance to the targeted drugs currently available will be developed.

Cheers,

Cindy

[mariootsi]

I have been taking pantoprazole for years. Not sure I understand how it affects Ibrance.

[mariootsi in reply to mariootsi]

Ok So I read all the articles from Eduardo and Sandra. I get it! I'll have to speak with my onc about my PPI! But, I have to take something for my acid reflux!

[mariootsi]

Thank you so much Sandra. Good luck to you too. We are both on PPI!

[NPmary]

Thanks for the info but l don't see in your post the article titles. Please respond withe titles or a link to them. I'm sorry your wife had to change her treatment. Take care.

[Evbr in reply to NPmary]

1. Drug-drug interactions between palbociclib and proton pump inhibitors may significantly affect clinical outcome of metastatic breast cancer patients

2. Overexpressed cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors

[NPmary in reply to Evbr]

Thank you

[NPmary]

Thanks, Sandra! I appreciate this ❤

[Contrarielle]

Thanks for sharing Eduardo- food for thought as since on palbo I've had bad reflux. Enough to give me night time choking & coughing and sore throat. I am trying domperidone mostly to help with gastric motility and will reserve PPI for desperate measures.

Good luck for your wife's treatment with Afinator.

[Hazelgreen]

You and Marianne may both be fortunate in not really needing palbociclib since a significant group of the original clinical trial subjects did well on letrozole alone (34.7% vs. 42.1% according to the 2016 paper: nejm.org/doi/full/10.1056/N...). Apparently, PPI's do not interact with letrozole.

It might/might not be worth your while to read this other 2021 paper: ncbi.nlm.nih.gov/pmc/articl... which concludes with the following comment:

"The risks and benefits of long-term PPI use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Although there are multiple reported system-related side effects of these drugs, in most patients with appropriate short-term indications, the benefits of PPIs are likely to outweigh the risks."