Ibrance (Palbociclib)
Comments
-
Nice video!
I have tried to ask before, but try again now... I am on 100mg Ibrance plus aromasin ... I am struggeling with anxity and derpression (about what will happening to my two small babies if I can not be there ....the yongestone is only one year... the other one 4,5)
Therefore I am taking effexor/venlafaxine as well...but I am afraid that the effexor reduces the effect of the Ibrance...
Anyone else on this combination, or that know something about this? My oncologists says that he have bot heard about it as a problem, but he seems not to know...
0 -
muddling through, Thank you for sharing it. I may have missed it, but are you you an Oncologist? I do want it to be shared anywhere that it might encourage other patients..
Tanya, nonahope and Lauren thank you.💞
0 -
Anna, I am so sorry that you're having to deal with this, especially at your age and with little ones. So scary.
It has appeared to me that Pfizer and the Specialty Pharmacies are the best sources of information about what should and should not be taken with Ibrance. Have you checked with them?
Good luck, sweet girl-
0 -
Grannax no, I'm a retired math teacher, at middle school, high school, and college over the years. My patient coordinator at the oncology center shares links with me and I send her select things too. She's about the only one there who will respond to me in between appointments! She was very helpful to me in getting the blood sample drawn and mailed for the MBC Project, and things like that. It's a small center and the two oncologists are very busy with every kind of cancer there is. I'd like to be at a top notch breast cancer center but I couldn't stand the big city aspect of it at all!
0 -
Me too, muddling through. I opted to stay local even though I could have gone to the big guns because they are close. I did go to MD A this time for their advice on treatment. I was also there for my second DX and with my DH. But this time, I'm older and alone. I just needed to do what is easiest for me and my family. This time at MD A it felt overwhelming, it didn't before. My MO here is young and sometimes I struggle with trust with her. But right now I don't have anything that's bothering me, when treatment change happens I might go down to MD A again, just for their opinion.
0 -
hi Anna,
Sorry that you have joined us but I think you’ll find a lot of great info on these boards.
I was immediately prescribed Effexor by my MO (and I am on Ibrance and letrozole (an AI) as well as Lupron injection and xygeva injections. I’m pretty sure that there are no negative interactions between Ibrance and Effexor, however, you may want to inquire with the oncology psychiatrist about antidepressants and anti-anxiety medications. I too suffer from anxiety and depression and just started on Lexapro, and I take Valium as needed.
Here is a post that is all about this topic, hopefully it will come in handy for you as it has been for me:
https://community.breastcancer.org/forum/8/topics/867583?page=1#top
Hugs!!!! Brenda
0 -
Grannax, you are such an inspiration. YES! YES to HOPE!!0 -
Hi all; I've been away for a bit and just catching up on all the posts. Sending hugs and love to everyone. May we all have wonderful results.
Grannax: I loved your video and will post it wherever I can. I didn't know this about liver mets and I'm sure many don't. Thank you.
Lauren; I wanted to tell you how wonderful it was that you shared your journey with hundreds at your work. Not only did you offer inspiration to those attending but staff will now know that the company supports women and men going through cancer. There may even be some who attended who were suffering in silence out of fear. Congratulations to you.
Anna; I'm so sorry that you are having to go through this with such a young family.....and even if you didn't just being so young. You will find lots of hope here and we are all behind you with all the support we can offer.
Pat; Thinking of you and we'll be waiting for the next positive scans. Hugs.
Cathy
0 -
Anna,
I don't take effexor. I do have anxiety, depression and insomnia. I'm able to use CBD THC oil combination, melatonin, and meditation. I did take the pain and sleep meds but they had so many SE coupled with what I was getting from the faslodex, ibrance, zometa, combination that I stopped. I didn't want to be addicted to the pain and sleep meds and they also made me feel sluggish and hung over. There's no chance to over dose with the CBD oil combination. Sorry about finding yourself here with such a young family. I hope that something I've shared is useful.
Tanya
0 -
Good to hear from you Seaway. Thanks so much for sharing the video. I've already had an indirect response from a family friend. Her husband has pancreatic cancer that spread to his liver. He's two years out and his TX is not working. We talked for a long time and they are going to contact my doctor. PTL
0 -
Boy, where have I been?! The San Antonio MBC conference abstracts went up online several days ago!!
Here is a link, just click in as a guest at the upper left and enjoy reading about all the latest and greatest! I will pop back in when I find something, anything, that sounds good..
https://www.abstracts2view.com/sabcs18/0 -
Two drugs I am keeping an eye on are CDK7 and CDK12 inhibitors. Not yet much in clinical trial, but here is a Dana Farber abstract of preclinical studies saying that CDK7 inhibitor (SY-1365, which is currently in clinical trial but is injection, there is an oral pill making its way onto the trials) works against MBC that has become resistant to Ibrance-Femara. Is being tested in combination with Faslodex, but you pretty much have to be first or secondline...
Inhibition of CDK7 overcomes resistance to CDK4/6 inhibitors in hormone receptor positive breast cancer cells
Background: Despite the efficacy of the combinations of endocrine therapy (ET) and CDK4/6 inhibitors in the hormone receptor positive (HR+) metastatic breast cancer (BC) setting, the majority of patients eventually acquire resistance to these treatments. The loss of Rb activity is an important mechanism of acquired resistance to CDK4/6 inhibitors. Preclinical and clinical data support the RB1 genetic aberrations, including mutations and deletions with loss of expression, as mechanism of palbociclib (palbo) resistance. To study vulnerabilities and potential treatment targets to overcome resistance to CDK4/6 inhibitors associated with Rb loss we studied a T47D palbo-resistant (T47D PDR) HR+ BC cell model obtained by exposing palbo-sensitive cells to increasing concentrations of palbo. These cells harbour deletion of RB1, and show increased cyclin E1 and decreased ER expression.
Methods: To identify genes that are essential for cell growth and genes whose loss enhances cell growth in palbo-resistant cells with loss of Rb, we performed genome-wide CRISPR-Cas9 knockout (KO) screens in T47D palbo-sensitive (T47D PDS) and T47D PDR cells. We searched for significantly essential genes that are targets with available drugs and tested the efficacy of these compounds in T47D PDS and T47D PDR cells.
Results: By employing a genome wide CRISPR KO screen, we identified 29 genes that were significantly positively selected in the T47D PDR cells. Among these genes were known tumor suppressor genes, such as TSC2 (β score: 0.89) and PTEN (β score: 0.68). We identified close to 600 genes that were significantly essential (negatively selected) for T47D PDR growth. CDK4, CDK6 and CCND1 were essential in the T47D PDS parental cells but lost essentiality with the acquisition of palbo resistance (FDR> 0.05). CDK7 (β score: -1.21) and CDK2 (β score: -1.67) were among the top ranked essential genes (FDR: 0).
CDK7 is a transcriptional CDK and has CDK activating kinase (CAK) activity. The CAK activity includes phosphorylation of CDK2 and CDK9. To follow up on our CRISPR screen results we tested the activity of the selective CDK7 inhibitors SY-1365 (currently in phase 1 clinical development) and THZ1 in the T47D PDS and T47D PDR cells. We saw dose dependent activity in both cell line models. Moreover, the IC50 values were comparable in T47D PDS and T47D PDR cells (THZ1; PDS: 9.93 nM, PDR with Palbo: 32.8 nM, PDR without Palbo: 1.08 nM) (SY1365; PDS: 1.60 nM, PDR with Palbo: 6.70 nM, PDR without Palbo: 1.87 nM). Combination studies of SY-1365 and fulvestrant in T47D PDR showed synergistic activity at lower concentrations.
Conclusions: In a model of palbo resistance with loss of Rb we found that cyclin D1, CDK4 and CDK6 are not essential, suggesting cross-resistance to other CDK4/6 inhibitors in this setting. We identified CDK7 as a significant essential gene and potential therapeutic target. We validated these findings with the selective CDK7 inhibitors, THZ1 and SY-1365. Our results offer a new therapeutic strategy for the treatment of palbo-resistant HR+ BC.[Note: No info yet on the early trial, so we have no idea of how well it might work, or the possible side effects]
Session: Spotlight Session: Lobular Breast Cancer (7:00 AM-9:00 AM)
Date/Time: Friday, December 7, 2018 - 7:00 am
Room: Stars at Night Ballroom 1 & 20 -
Thank you! I was just thinking of looking that site up for updates on the abstracts.
The brain mets studies alone sound hella interesting...
0 -
Interestingly the Alpelisib phase III trial, SOLAR-1, abstract has been embargoed until Dec 6; we know the drug is heading for FDA approval, but it will be very interested to hear the updated PFS and other information about this drug- is for cancers that have progressed on Ibrance-Femara due to a mutation in the PI3K kinase ( a very common mutation that arises when MBC escapes firstline drugs and becomes endocrine-resistant)
0 -
Cure-ious, have I told you lately how much we appreciate the big jolt of hope you give us with these posts? Thank you so much.
Love from PatGMc
0 -
Just trying my little bit that I can to give back to everybody here who helps me everyday, Pat!! And one day, it will just be to pay it forward, when all of us are stable and happy!!
I did read where about 30% of Ibrance users may notice that old lymphedema start to come back, is also a side effect newly noticed for mTOR inhibitors, so if anyone here has noticed some swelling that they thought was long gone, it could be the drug.
Another abstract says that cancers with ESR1 mutation (estrogen receptor mutated so its active even in absence of estrogen, which happens in almost 40% of the cases when the cancers become endocrine resistant) have upregulated the CHK1 kinase, so those cancers might do well with CHK1 inhibitor drugs (in trials) or also the CDK7 or CDK12 inhibitors noted above, which also work on that pathway..
one study looking at mutations that are new drivers of cancer growth that appear upon progression on Ibrance-AI found:
"The most common acquired alterations at the time of progression that were not present in the pre-treatment specimens included mutations in ESR1 (30.3%), TP53 (30.3%), RB1 (12.1%) and PIK3CA (9.1%), and FGFR1 amplification (27.3%)."
So, interesting that ESR1 mutations were more common at this stage than PIK3CA mutations, the latter of which eventually appear after multiple drug treatments and respond to Alpelisib...
0 -
Very interested in the ESR1 info. I have that one. Thanks for the info.
0 -
Somebody tested the effects of a daily 100mg Ibrance dosing schedule, but the level of grade 3/4 neutropenia (neutrophil cell count drop) was worse (higher) than what they see for the 125mg Ibrance on the normal schedule..
0 -
Hello everyone! It's been quite a while since I've checked in. Nice to catch up with everyone.
Jaycee49 - Glad your eyes are healing; hope they continue to get better quickly!
PatG--sorry that you had some progression. You are an inspirational person! Hope that all goes great for you! I was interested in your comments about Rational Emotive Behavior Therapy. I may have to look into that.
I have been experiencing anxiety lately more than normal. I had never experienced anxiety until my diagnosis in 2008, but it only appeared once in a while. Since I've been on Ibrance (9 months), the anxiety is much more frequent. So I've been looking into ways to manage it.
And welcome to the several new folks on our site!
Hugs!
Debbie0 -
Debbie, I haven't signed up for this website. I know some sites claim to be free and as you move along, you find there is a charge. All that said, you might try to read some of the literature on REBT here. Albert Ellis is the main guy. There are things about his writing that go against my beliefs but the basics of rational emotive therapy are sound...at least, they worked for me. I hope you find this useful:
https://www.researchgate.net/publication/274381619...
Love from PatGMc
0 -
Cure-ious, thanks so very much for your vigilance and explanations!
0 -
Hi Anna - I take Ibrance and Effexor (75mg) and my onc says there is no interaction. I take it for mild depression and it helps a bit with hot flashes.
Cure-ious - I love it when you alert us to new information. Bless you! I did get Lymphedema in my hand 6months into Ibrance, after being stable in that arm for nearly 15 years. I had a feeling the drugs were behind this but I was blaming Faslodex.
Seaway - so nice to see you! Thanks for your feedback. I’m amazed but I have gotten so much feedback from folks who are struggling with various medical issues at work and told me they feel so much less alone. That makes me happy.
Love to all,
Lauren
0 -
Cure-ious: I really appreciate your great knowledge and the time you spend on researching and providing us with the latest news. With respect to the mutations you mentioned in your post, can you provide a linkage as to which meds are available/under research for each of those mutations? My chemo brain is not able to remember/connect all those bits and pieces that I read earlier on the mutations/correlating meds (I hate that, it makes me feel so stupid, especially since this is rather closely related to my everyday work).
0 -
I went from 30 cycles of Ibrance/Femera onto the BYLIEVE trial which is Alpelisib with fulvestrant (or letrozole) but I had progression on letrozole so am on the other arm. Ibrance/Femera was a very easy combo for me. I had very good quality of life.
I was on alpelisib 300mg for 10 days before the really severe SE's kicked in. Nausea, vomiting, general feeling of being extremely unwell, hives, headache, diarrhea, SOB, you name it, I had it. They held the drug for 4 days, so I was feeling better again they said I had a stomach bug, that it wasn't the drug.
Restarted the drug & within 20 mins, my body was covered in hives, another 20 mins the vomiting & diarrhea started. That lasted all night, the hives lasted for 4 days. Apparently none of this is a case for not taking the drug, perhaps a dose reduction. DH wasn't sure how he was going to get me home, as we have to travel 6 hours to get to my cancer centre. I feel like a lab rat. This is only my second line of treatment, I shouldn't feel badly should I?? I'm not sure what fresh hell they have planned for me, but please, if you are thinking of doing this trial, please read about all the side effects before deciding. I did read them, but never thought I would have every single one of them.
0 -
Oh No!! Hope they help you reduce the SEs soon...misery is hard to do. Sending warm hugs to you
0 -
GG27, would your MO consider doing Kisquali (Verzenio) + Fulvestrant instead? This is what I’ve been told will likely be my next treatment once progression on I/L occurs. The three CDK46 drugs target differential stages of the cycle, so there is thinking it’s possible to move on to one of the others
0 -
Thanks Kathryn. My SE's are gone at this point because I'm off the drug for 2 weeks. Next Tuesday is the next time I see MO, not sure what she has in mind.
Jen, I don't believe that Verzenio is available here in Canada yet. I plan to ask what my alternatives are.
cheers, dee
0 -
Thank you all for answearing me! It means a lot! I live in a small country and there arent many to find in the same situation.
And...some of you mentioned CBD oil... actually that is not legal in my country (yet)
Wish you all the best
0 -
Hi Netta!! Great to hear from you, how are you doing?!!! I just got back from work and am about to go deep-dive into the SABCS abstracts again, but will try to make a simple chart as you suggest
GG27- Alpelisib seems like a potent but difficult drug to tolerate- if you have the PI3K mutation, it at least is no doubt doing you a lot of good, for however long you can stand it. They have been playing around with the dosing schedule, in addition to the levels. I wish the trials would just test which of the possible different partners for Faslodex ( eg Ibrance, Alpelisib, CDK7 inhibitor, or checkpoint inhibitor) works the best as a secondline therapy. even if it turns out you have to ditch the Alpelisib, at least you very likely got some benefit from having taken it. Just plain Ibrance-Faslodex should be an alternative, because most cases where resistance has happened it is because the cancer mutated to escape the Femara, not the Ibrance...
0 -
Without picking any examples, there are quite a few abstracts talking about various SERDs, which are compounds that promote the destruction/degradation of the estrogen receptor, just like Faslodex does- with the exception that SERDs are oral (pill, not an injection) and therefore they can use higher levels of them. Several studies of different SERDs are showing that they also degrade the common ESR1 mutant forms that arise after AI treatment and lead to progression, and also that they have effects in cancers with PI3K mutations. No idea why so many of these trials still seem to be phase 1 or even pre-clinical, as it seems these drugs have been in development for a long time...
0
