Ibrance (Palbociclib)
Comments
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Cure-ious,
Thank you so much for posting both the link to the article and the explanation. I just read the article and sent an inquiry to the corresponding author at UCLA (although I realize that it's a long shot that he will or will not respond.). I have my three month CT scan on Tuesday, and although my scans last time showed stable disease, my tumor markers have been climbing. Although I have 25+ mutations according to my Foundation One report, PD1 and PDL1 are not listed on that report. I do, however, have two ERBB2 mutations. It does puzzle me why Ibrance/faslodex may not be working for me because I don't have an ESR1 mutation. Also, my F1 report listed atezolimumab (immunotherapy) as one of the drugs that could be beneficial to me. So it will be interesting if the author weighs in on the ERBB2 mutations and how they may affect the efficacy of I/F combo. We shall see....
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Thank you Pats granddaughter for allowing her to share your literary and artistic Prowess. Pat you are both gifted artists. Very nice. What she described comes through in your humorous, encouraging posts.
Tanya
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Sandi- Interesting what you posted about the MRI for liver mets. I wish I could ask for a second opinion concerning MRI, but I am established with this MO and not planning on changing MO's (at least not till progression). So I guess I need to trust her on the scanning protocol. We have been doing CT's all along. And never MRI's. So comparing from scan to scan for changes, I guess need to stick with CT's. Doing a MRI now would have nothing to compare it too, right?
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BevJen,
I'm so excited by that paper, having wondered for years what makes a strong or poor response!
One thing tho, don't mix ERBB3 (associated with a good I/F response) with ERRB2 (HER2) they are different, and in fact high active ERBB3 is associated with poor response to HER2 inhibitors (for those who express both genes)
I'm going to go geek out on what it means to have high ERBB3 and FGFR2 expression (and if they are linked to low PD1 expression) and will make another post.
Also its important to remember this paper is looking at samples before treatment; so it doesn't have any meaning for what happens at progression, that is a different kind of analysis. There might be more Rb loss after treat with I/F, for example- some mutations only pop-up at progression.
PS If you have a report indicating that you should respond to immunotherapy, I would definitely try to get in to an immuno-I/F trial, it seems that there are multiple of them now!0 -
Just should be mentioned that it has also been reported that FGFR1/2 mutations can be associated with RESISTANCE to I/F. More research needed, obviously other genes are also involved in determining the outcome...
https://www.nature.com/articles/s41467-019-09068-2
On a different topic, CDK4,6 inhibitors were picked up in a blind screen for compounds that make immunotherapy work better, in part by affecting immune cell activity. It would also be helpful to know if women treated with Ibrance show increased PD1 expression, or how to increase PD1 expression and responsiveness to immunotherapy
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Cure-ious thanks very much for once again posting useful and interesting information. Like BevJen I often contact a researcher or author about information with varying degrees of success. However, this time I sent the aacrjournals one straight to my Onc - something for him read on a coffee break😂. He at least always responds
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Cure--ious,
I am still waiting for F1 results, but did get PDL1 result.. negative. PIK3 negative, too.
Is that the info you were looking for? I was on Ibrance 39 months. I did not have F1 at dx in 2016.
S
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Thanks Cure-ious for the articles. Not good for me because my Oncopanel mentioned about "single copy deletion of RB1" does this mean I will be resistant to Ibrance soon?
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Cure-ious
What is considered mine said PD-L1-Low RNA expression score: 19. ?? The ONC said no actionable mutations.
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Hello,
I am cross posting with the Xeloda thread to see if anyone has similar F1 report.
After progressing on I/L, I had a liver biopsy and F1 done.
I am still ER+ and HER2-. I am negative for PIK3, PDL1, ESR1, BRCA1/2, ERBB2. No reportable alterations.
MS-Stable, Tumor Mut Burden 3 (ATM Inversion exon 55, FGFR1 amp, GATA 3 plus few nonactionable others.) Recommended clinical trials: PARP inhibitors...???what??
ATM therapies with clinical benefit: Olaparib, Talazoparib, none for FGFR1
So why did I progress on Letrozole (and Ibrance)? What is driving the cancer now? I am confused.
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I asked last time I had my appointment if they did a foundation report and they said no they normally wait for progression. Is that normal? Also, I have low her2 expression, but not enough to classify me as her2. Does that article mean I should not do well on ibrance? Thanks curious and everyone else for sharing all you knowledge.
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Simone, my MO did not order F1 at dx either. She said it would not change the treatment plan. But I would have it at progression when more mutations would be discovered or can be tested.
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BevJen, you said above, “I do, however, have two ERBB2 mutations. It does puzzle me why Ibrance/faslodex may not be working for me because I don't have an ESR1 mutation.“
Based on my research, the ERBB2 mutation is quite possibly the reason.
https://www.nature.com/articles/s41588-018-0287-5
“Examination of treatment-naive primary tumors in five patients showed no evidence of pre-existing mutations in four of five patients, suggesting that these mutations were acquired under the selective pressure of ER-directed therapy. The HER2 mutations and ER mutations were mutually exclusive, suggesting a distinct mechanism of acquired resistance to ER-directed therapies. In vitro analysis confirmed that the HER2 mutations conferred estrogen independence as well as—in contrast to ER mutations—resistance to tamoxifen, fulvestrant and the CDK4 and CDK6 inhibitor palbociclib. Resistance was overcome by combining ER-directed therapy with the irreversible HER2 kinase inhibitor neratinib.“
This seems to be the case for me.
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SP,
Thanks for that info. I know that we've kicked that around before. I was responding mostly to what was in those articles that Cure-ious posted, which seemed to focus on the ESR1 mutation. I guess I should have thought through more thoroughly what I was writing, given that information. Also, my head is full of lots of questions, given my consult this week with Dr. Cristofanilli and my own scan at Hopkins.
Too much info. Too little time.
Thanks much.
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Sandi, I am cross posting what I said on the Xeloda thread: I think your F1 report suggested PARP inhibitors because of the ATM inversion, ATM being related to BRCA1. Whether the mutation is germline or somatic (just a mutation in the cancer), PARP inhibitors may work.
BevJen, I know right? Sometimes my head is so full of information and questions that I feel like a juggler with too many pins in the air. This is an important consultation coming up for you and and important scan.
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I asked my MO at my appointment this morning about the Foundation one report. She said she didn't order it because I didn't have enough tumor from my biopsy for it. They would check this if possible when I progress. She did tell me they are starting to look at her2 drugs for other mbc patients.
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BlueGirlRedState - I don't take any iron supplements. My blood counts were normal before Ibrance. Then my RBC started going down. It went below normal after 2 cycles and continues going down. I already eat beef and spinach, but I'll pay more attention to my daily consumption.
For scans so far, I've had one CT scan during cycle 4 (at 6 now). I still feel scanned out after having all sorts of scans trying to find the reason for my high TMs. I don't mind waiting. As long as my TM is going down, the blood check is enough for me.
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So I have no answers except for 42young, losing one copy of RB should have no effect on your response to Ibrance, deletion refers to losing both copies, with one copy you have half the normal level, but in fact when one copy gets deleted of a gene its common for the other gene to increase expression and make up for it, if its important for the cell. The paper says different levels of RB had no effect.
I have not had any genomic testing (beyond ER+/PR-/Her2-) so I was wondering if these reports looked at levels of HER3/ERBB3 or FGFR2? I'm almost at five years so if my next scan is stable I'm going to assume I've got FGFR2, ERBB3, or both, But who knows how many other genes also contribute to a Ibrance response?
Her3 is not as simple to block as HER2, but people have been trying. There is no FDA-approved drug I can see, but some monoclonal antibodies and ADC-conjugates. But it seems the clinical trials just keep getting dumped without comment, so maybe its really toxic.
This paper is looking at mutations in the primary tumor that might predict whether you would do well on Ibrance, or might already be resistant. It's not looking at what changes happen in the cancer that make it progress after some time of response.
Sandi, the FGFR1 they are trying to find drugs against. FGFR2 is highly related, and as I mentioned has been associated with response to Ibrance but also as making cancers resistant to some chemos. It's so frustrating wanting to see what changed that made the cancer stop responding.
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Although these early stage drugs often lead nowhere, I find it hopeful to try to keep track of how they are doing. Here is a new Her3 antibody, developed by Hummingbird in Asia, they are collaborating with Cancer Research UK to bring it to clinical trials, once trials ever get going again with COVID. They published data showing that it works better than earlier Her3 antibodies, which did not effectively inhibit.
Her3 is overexpressed in about a third of MBC, and increasing Her3 is one route by which Her2-positive cancers can mutate to escape Her2 drugs, so it is an active area of research.
https://www.prnewswire.com/news-releases/hummingbi...
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Cure-ious, Thanks again for the interpretation. I hope Ibrance will keep me stable for few more years. Good luck with your next scan!!
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Tablets vs Capsules. So far the smell and no food requirement have been mentioned on these posts. I just got my first package, which I will start in June. Has anyone noticed other differences. With the capsules, the Pfizer literature seems to show a considerable difference in absorption with calories and fat content of meal. So what was changed so that food no longer needed and does it affect how well absorbed? Maybe a question for the pharmacologistr.
SerenityStat - just saw the PA yesterday and asked about low blood counts, iron etc. Maybe it was someone else who mentioned iron, iron suplements ? She she said my hemoglobin (iron content) was fine, so what ever I am doing (nutrition), keep doing it. My blood counts remain low, but within acceptable levels. Considering tumor shrunk 2.3 cm Sept 2019 to 7mm April 2019, Ibrance is working.
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I was in the middle of round 3 of Ibrance, and my WBC went from 2.8 to 2.1. The oncologist was also concerned because
my Absolute Segmented Neutrophils was 0.52 th/mm. Healthy is 1.40 - 7.00 th/mm3
My oncologist said to stop taking Ibrance (I had 9 left at 125 mg) and start up again after the 9 days plus the week off. She is lowering the dosage to 100 mg from 125 mg.
I just want to check with you folks. Has this happened to you? Feeling bummed.
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Woodlands - oh yeah, same thing happened to me. My first month out I was fine at the mid-month check but by the end of the month I was a hair under the 1 line (WBC? Neutrophils? forgot what the magic number is) and complaining of some side effects so they just dropped me down right away to 100 and didnt faff around with another month at 125. Even though I knew, reading this thread, plenty of ladies were just fine on 100, 75 or 75 + extra weeks off (lookit Karenfitzbo!) its this weird mentality like you failed. Or maybe its a fear like oh no, maybe this is the first sign that my body cant handle this drug. But Ive been on 100 the last 5 cycles, feel great (well, outside the back problems) with limited side effects, and my bloodwork looks good/is steady to the point where I now do bloods every other month.
I also imagine in this Covid world they are going to be a LOT more careful if things are trending in the wrong direction.
Just ride the bummed feeling for a day or two and then get back on the horse - it passes, trust me!
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Woodlands try not to worry, everyone reacts differently. The Paloma trials were based on 125mg and there were drop outs because folk couldn't tolerate the dose, but they had to maintain 125mg to verify the trial. Many of us are on different regimes, as Sondra says, I very quickly had to drop to 75mg and even at that bloods were taking over a week to recover pretty much every cycle, so we extended to 2 weeks off. I've been NED for a year and a half and I figure that my body just needed to find it's level. It wasn't too much of a surprise as when I had chemo in 2007/8 they had to reduce dose and shorten the number of cycles as the toxicity was too much. I just see myself as a good reactor, long may that last!
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Hello just a quick response I was on a Paloma trial and was started at 125mg . I requested to drop to 100mg although I was fine on 125mg The Oncs were very happy saying that big Pharma do phase 1 trials to assess highest tolerability but that they would be happy to start everyone on 100mg. I do think that we are all different and very lucky to be able to massage the dose to suit us
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Woodlands - I think everyone will be a little different, and DRs response might be different as well depending on the overall paitent health, the DR knowledge/experience/opinion. My WBC dropped immediatey with Ibrance, from 7 before Ibrance to about 2.1 now. Just finished Cycle 8. My DR says it is low, but within acceptable range of someone taking Ibrance. The Absolute Segmented Neutrophils (ACT) does not seem to counted, unless it is being called gran% (51) or gran auto (1.3)?. They both dropped with Ibrance. 125 mg capsules since Sept 2019, tablets start in June. DR has not indicated any need to stop or lower dose.
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I had my CT scans today. Awaiting results. I know progression will come at some point, but I don't want it to. Will start cycle 30 of Ibrance (first line therapy) next week if all still ok.
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Candy-678: glad your scans are behind you once again. Keeping fingers crossed for only good news with the results
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Candy, praying for good results. None of us want progression of course.
My liver ultrasound showed the new tumors are too small and unsafe to biopsy so I am waiting for a decision on next meds. I had four years on IL as a first line treatment so I feel blessed. Hope you have at least as long.
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Candy, sending you positive energy and prayers for good results on your scan:)
Woodlands, I know how you feel
I felt somehow defeated when I was bumped down to 100mg due to consistently low neutrophils from Ibrance. Even at 100 mg I had to delay 5 days to start. I take a lot of comfort from Chico, Karenfizbo15 and others that have had continued success or stable results on 100 mg or less. I really would like a Foundation1 test - my onc won't do one as my cancer center ordered a UW oncoplex test which she said is similar and showed I don't have the pik3ca mutation. I will try to get a copy of the oncoplex to see what else (if anything) it shows.
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