Ibrance (Palbociclib)
Comments
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I thought this one was interesting- treat oligometastatic patients (1-5 individual mets only) with radiation (SBRT) and immunotherapy. 80% had PFS at nine months (is not a long study thus far) and three remained progression free at two years, all of those were luminal cancers (not TNBC or HER2-positive)
Safety and efficacy of stereotactic body radiotherapy and Pembrolizumab in advanced breast cancer patients with 1 to 5 metastases
David SP, Savas P, Neeson PJ, Luen SJ, Foroudi F, Siva S, Loi S Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Olivia Newton John Cancer Centre, Melbourne, Victoria, Australia
Background
Pre-clinical studies have demonstrated that stereotactic body radiotherapy (SBRT) induces immunogenic cell death and tumor antigen release promoting anti-tumor immunity. We hypothesized that the efficacy of SBRT could be improved with the addition of PD-1 blockade in advanced breast cancer (BC) patients with oligometastatic disease.
Methods
Advanced BC patients with 1 – 5 metastatic sites of disease received SBRT at a dose of 20Gy in 1 fraction to at least 1 metastasis followed by pembrolizumab 200mg IV (within 5 days of SBRT), once every 3 weeks for a total of 8 cycles. The primary endpoint was safety of the combination. The secondary endpoints were response using RECIST 1.1 and PERCIST 1.0 using 18F-Flurodeoxyglucose (FDG)- positron emission tomography (PET) scans as well as local progression-free survival and distant progression-free survival (d-PFS). Correlatives included deep sequencing of the T cell receptor (TCR) CDR3 regions of archival metastatic tumor material and in peripheral blood as well as evaluation of systemic markers of immune activation.
Results
15 patients were enrolled between March 2016 and Nov 2017. The number of patients with 1, 2, 4 and 5 metastases treated with SBRT was 9 (60%), 3 (20%), 2 (13%) and 1 (7%), respectively. There were 3 (20%) TNBC, 2 (13%) HER2+ and 10 (67%) ER+/HER2- (Luminal) BC patients. Five (33%) patients experienced Grade 3 or higher Aes. Immune related Aes were reported in 10 (67%) patients, the most common being rash (n=4), thyroid (n=3) and pneumonitis (n=3) with pembrolizumab delayed in 3 (20%) patients and discontinued in 2 (13%) patients. Nine (60%) patients had a complete response or partial response according to RECIST 1.1 criteria and 13 (86%) patients had a complete metabolic response (CMR) or partial metabolic response (PMR) according to PERCIST 1.0 at the 3-month FDG-PET scan. At time of reporting (median follow-up 15 months; range 9-26 months) no deaths or local progression have been observed. Five patients (33%) progressed distantly at 3, 8, 8, 12 and 18 months: 2 of 3 (66%) TNBC, 2 of 10 (20%) Luminal and 1 of 2 (50%) HER2+. Estimated dPFS at 9 months was 80% (95% CI [62% – 100%]). Three patients have reached the 2-year mark without progression (all Luminal). In a patient who remained progression free at 24 months, TCR profiling showed that TCR sequences in a pre-treatment metastatic tumor biopsy were found in peripheral blood and became elevated after combination treatment, along with the emergence of new TCR sequences not seen in the tumor sample. Markers of increased CD8+ and CD4+ T cell activation using flow cytometry of peripheral blood lymphocytes were observed. This data suggests that the treatment induced peripheral expansion of tumor-specific T cells in this responding patient. Further correlatives are pending.
Conclusion
The combination of SBRT and 6 months of pembrolizumab in advanced breast cancer patients with 1-5 metastases showed an acceptable toxicity profile and promising clinical benefit especially in Luminal BC patients. Evidence of peripheral anti-tumor T cell responses was observed in a patient who remains progression free at 24 months. The potential synergy between these treatment modalities requires further study.0 -
plus one abstract says that using faslodex alone as a secondline treatment gave only 4months of PFS, and it went even less than that if Ibrance was used in the first round- so at least we know that faslodex needs to be partnered with something else for secondline treatment
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PatG - Thanks so much for the link! I will check it out.
Hugs!
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Hello Ibrance dancers,
Been checking off trips and adventures from my bucket list... I like to check in here every so often to see how all are doing when I am settled back at home. Sorry to see new members, but know that this is the best place for support and to gain insight. Ibrance has been relatively tolerable for so many and with good results!
PatG - I am in the JALP crew with you... I like that term. Sorry to hear you're experiencing it also
But we are still here as you said!Just switched over to Faslodex as of today (from 14 mos. on Letrozole) Hoping the I/F combo will knock back these stubborn lung mets. They've been growing a few mm each month since April - so it was time. We biopsied and determined still strongly ER+ ...Waiting on genome sequencing results to see what has changed to make it resistant to Letrozole. Originally I tested negative for ESR1, pik3, Tp53 etc... (I do have a large PALB2 deleterious mutation though, so perhaps that is what is driving things, PARPi is on my radar)
Thanks to Cure-ious' SABCS abstract info I always feel armed with the latest news to ask my MO. Really appreciate you sharing your findings with us Cure-ious! I'm looking forward to perusing through all of the data. Interesting about the Oligio/SBRT/immuno abstract. I wish I had qualified for SBRT... too many nodules appeared after we thought I was oligo initially.
GG27 the trial sounds rough! Sorry to hear you're having such a tough time with it. Will you try to switch to Ribociclib/Faslodex? I'm across the water from you... Been keeping my eye on Verzenio being approved also. I don't know that it has been submitted for review yet though. Hopefully soon!
A while back I recall reading Jaylea or another J was having issues with vocal chords? I hope that has resolved.
Would love to hear from others who had mild progression on Letrozole/Ibrance but then later found stability once they switched to Faslodex/Ibrance... I hear Faslodex is more effective so I am trying to remain positive. My butt sure hurts after those two shots!
All the best to everyone. Xo
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Ashlyn, I've long felt that PARP Inhibitors are what my mutated self (BRCA1) will need one day. Now that a second one has been approved for MBC, I'm feeling it even more. And I'm thinking it's a Pfizer drug! Maybe one day we can take it together though I bet we end up with PFD again on Ibrance! That's my prayer for all of us. (one day we'll fondly speak of the old days when we were JALP.)
Love from PatGMc
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Ashlin I’m sorry that letter is all stopped working for you. I have been off as faslodex and Ibrance since February 2018 and it cleared my lung nodules and pleural effusion and my bone Mets up so it’s a pretty good combination. I hope it works as well for you as it did has for me.Have you been on the Faslodex thread there’s a good list of things to do to kind a help with the hurting of those shots. plus joinery found out that if you take Claritin two days before your shot the day of your shot and two days after it helps. I’ve been doing this and it really helped me I missed one time and I regretted it afterwards.
Curious thank you for all of the great information. when I first started this I didn’t have a clue where to go or what to do and I thought of the Ib and Faslodex not working one day really scares me but with what you tell us and gives me hope that there are plenty of treatments out there and new ones coming.
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hi everyone!
Just curious if anyone has had a high a/g ratio result in their blood work and if that was concerning to your MO?
My recent bloodwork is showing a high a/g ratio and low alkaline phosphatase.
I know that the meds can wreak some havoc on our bodies, but this is a new one for me.
Thank you in advance!!!
Hugs - Brenda!
PS I have my monthly MO appt today so I’ll be going over all this stuff at my appointment, too. Just curious if others have seen this! Thanns
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Cure-ious, Thank you, thank you, thank you for posting the link and info from the SAMBC conference! Lots of much needed and interesting info.
I haven’t been able to find the study you mentioned about the effects of a daily 100mg Ibrance dosing schedule and neutropenia. Do you have the date or title of that presentation? Really want to talk to my MO about it.0 -
Cure-ious;
I'm very interested in a session as follows as I have a BRCA VUS and genetic testing of my tumour showed I have a P53 mutation as well. Do we just wait till December to look for the report? Sorry, I haven't used this site before.
ES12-3 BRCA 1/2/3 and p53 in replication fork stability
Schlacher K UT MD Anderson Cancer Center, Houston, TX
Genome instability is a hallmark of cancer, whereby the vast majority of cancer mutations are caused by defective DNA replication processes. BRCA and p53 genes are critical breast cancer suppressors and "guardians of the genome". Genetically, BRCA and p53 are frequently found co-inactivated in breast cancer patients. The predominant molecular gene functions ascribed to BRCA genes lies in DNA repair, while p53 is best understood for its transcription activities. Yet these respective functions are insufficient to explain cancer patient genotypes and phenotypes. Recently, novel roles for BRCA and p53 genes in stabilizing DNA replication forks that are separable from their canonical functions have been described.
During this session, we will review BRCA-p53 genetic collaborations during embryogenesis and cancer, with focus on their functional convergence at the level of DNA replication fork stability. We will further discuss BRCA/p53 DNA replication functions as critical new and distinct aspects for cancer therapy approaches and patient variant prediction.
Session: Educational Session 12 (5:30 PM-7:00 PM)
Date/Time: Tuesday, December 4, 2018 - 5:30 pm
Room: Stars at Night Ballroom 4-3rd Level0 -
Cure-ious;
Also, my MO seemed surprised that I have the P53 mutation and I wondered why. We didn't have time to talk about it and I won't see him again until January so if you or anyone else has any information on this I would appreciate it.
Thanks Cathy
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Cure-ious. Thanks so much for all that good info. I bet some of us will benefit from that at some point in our futures.
I can't remember if you saw my video. It's posted on here and on liver mets, y90 etc thread. I'm curious to hear what you think about it. I also wish Z could see it.
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Cure-ious, it would be great if I could do faslodex/ibrance but it is not funded here in Canada, neither one. And not available on a trial.
I appreciate the sentiment that alpelisib could be doing me some good, I'm not sure. When I throw it up 30 mins after taking it, and have so many SE's, it's hard to see the benefit. I will see what MO has to say on Tuesday. In the meantime, I am enjoying feeling "normal" again.
cheers, dee
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GG27;
You don't mean that Ibrance is not funded in BC surely. It is covered here in Ontario by the government. I have no experience with faslodex but I notice it's listed on the Government of Canada site so if it's not funded there could that be just the BC government?
Cathy
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Seaway: Faslodex is only funded as a first line treatment in BC. Not as a second line. So the only way to access is through a trial or if you have extended benefits through an employer (which I thankfully have)
GG27: is it possible to try to get compassionate access through AstraZeneca? Worth it to try?
Holmes13: so happy to read you’ve had good results on the Faslodex/Ibrance combo. I’ve read about Claritin helping with rash etc. But it sounds like it also helps with pain and swelling too??? I will have to give that a try for my next shots. Feeling pretty sore today.
PatG: Nice to have PARP inhibitors in our back pocket. They sound very promising! I’ve seen quite a few women experience NED with Lynparza.
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Seaway, Ashlyn is correct, fulvestrant/Faslodex and Ibrance/palbociclib are both only funded as first line. As I just came off first line trial with Ibrance and Femera, I am not eligible for funding for either.
Ashlyn, I will ask my MO on Tuesday if we can try getting compassionate funding. I'm not sure what the next line is supposed to be, she told me a few months ago that I still had 8 lines of treatment left, but now all of a sudden when I'm not tolerating this trial drug, I'm in line for chemo only??? Do you know what the next line is supposed to be? ER+ PR+ HER2- It's so frustrating, my bone mets are stable & supposedly I have one tiny liver lesion that is suspicious for mets, it's not even confirmed.
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Dee- SusaninSF posted today on the lung mets site that she got 40% reduction in her lung mets after just two months on Alpelisib, and I've seen other reports that the drug often works really well right away, no need to wait six months to show benefit, however for some people resistance can develop quickly and, more often, people leave the trials due to the side effects.Maybe Susan has some tips. There is a paper in Nature that says driving down your blood sugar levels make it work much better, which can be done by fasting (water-only) for 12-14 hr at night, so I don't know if you tried that but obviously a lot of people have had problems with the drug.Now that the trial was declared a success I wonder if it will be FDA approved, in which case a lot of people will be trying it.
I don't get why you could only use Faslodex for first-line therapy, that makes no sense! At the least, it seems you could go onto Aromasin-Affinitor (some of the side effects should be similar to Alpelisib since these block the same pathways) or even Halaven? Agreed, you are too early to go to chemo- can you move to the US for a bit?!!
Seaway, I don;t know if it matters about the p53 mutation if the end result is it collaborates with BRCA mutation, anything hitting either part of the pathway should help. For BRCA mutations, PARP inhibitors are a must, not sure how they are used in combination or alone. Interestingly, mutation or inactivation of CDK12 causes a loss of BRCA expression, so in pre-clinical studies they have shown that a CDK12 inhibitor can be combined with a PARP inhibitor, and they both work much better on cancers that DON'T have a BRCA mutation. Therefore, perhaps all of us will be benefitting from the PARP inhibitors (in a combo with a CDK12 inhibitor). There are some overlaps between CDK7 and CDK12 inhibitors (the two kinases are pretty similar and cross-react with the drugs), so I'd keep an eye out for either inhibitor in trials.
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Cure-ious;
Thank you so much for this information. I don't understand why the CDK12 inhibitor combined with a PARP inhibitor work much better on cancers that don't have a BRCA mutation. I'm sorry but this is all very new to me. I really appreciate your time Cure-ious. It is interesting to think that the P53 confirms the BRCA mutation as I have wondered if the VUS was significant in any way.
Cathy
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Hi all - looks like I have a lot to catch up on from the last couple of days but I have a super quick question - is it grapefruit or pineapple (or both) that we need to avoid with Ibrance? My husband bought a fresh pineapple and chopped it up and I was about to eat it and then couldn’t remember which is ok
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It's grapefruit. And I also read pomegranate. (Not a 100% on the Pomegranate)
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With kisqali- no grapefruit or pomegranate. With letrozole-no grapefruit
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thanks all - I shall indulge
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GG- I remember Bestbird has a list of 2nd line options in her guide. I know there’s more than IV chemo. It seems to me Xeloda is one. Tha alsogives us a break so we can go back to cdk4 inhibitors later.
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GG27: hope that some of those suggestions above help with tolerating the trial. Great to see someone else having such a good response. If it’s too tough and you can’t get Fulvestrant I wonder if you could get on the Ribo trial? (Kisqali?)
It’s so frustrating that the BC cancer agency doesn’t fund Faslodex as a second line. I was told it is because the drug company submitted it for review as a first line only. They would need to resubmit it again to the pCODR recommending it as a second too. Same with Ibrance I believe. I think Rethink Breast Cancer is working to help change this.
Cureious: very interesting about the CDK12 in conjunction with a PARPi. Promising! I wish research could hurry up! hehe
LaurenH: it’s also Seville Oranges (I don’t know what those are. But they are on the no-no list for Ibrance)
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On Ibrance, I have heard that we should avoid grapefruit, pomegranates, and blood oranges.
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The problem with BB's guide is that it's for the US. I was hoping that someone in Canada, preferably in BC would have some idea. I will be able to find out next Tuesday, but will have to make a decision probably that day & would have loved some direction in where my MO's thinking might be.
As for SusaninSF, she isn't having nearly as hard a time as I am with the SE's, nor is the only other patient in the trial in Vancouver. I feel like a lab rat where they just don't really care how sick I am as long as they get their results.
Cure-ious, move to the US? really? I'm sure you were kidding.
not happening. It's hard enough traveling 6 hours each way to my cancer centre, let alone to the US. but thanks for the suggestion.cheers, dee
*edited to add. My blood sugar have been smack in the middle of normal. I eat low carb, very seldom do I eat dessert. I fast every night from 8pm til 10 am. Not really sure what more I can do on that front.
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OK ladies… after a lot of confusion and several pharmacies and my insurance giving me a hard time I have my Ibrance. I will be taking my 1st dose tonight. And now I'm having a panic attack lol. I get like this every time I start a new med. What has your experience been the 1st time you guys take this? Any throwing up? I know this is a very basic question but let me hear some reassuring stories 😂🤗
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Bubblebeard, It took a few days before I felt anything at all, and then only some fatigue and mild diarrhea. I actually feel better on the Ibrance/Letrozole combo than I feel on Letrozole alone. The SEs hit different each month: sometimes mouth sores, sometimes itchiness. I wouldn't fear it, but it hits everyone differently. I restarted Ibrance last night after being off for 3 weeks (pneumonia) and don't feel any different today at all. In fact, I have enough energy to do a little light housework. I have been on 125mg for 2 1/2 years.
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intolight... Thank you! That's one of the things that I was wondering , if this is something that kind of needs to build-up in my system before I even notice it. That is definitely reassuring, especially since I hear you've been on it for 2 and a 1/2 years! Awesome
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Dee- actually I do have an extra bedroom, you are welcome to stay anytime you want a trial in the US!
I think maybe YOU should become the "BestBird of Canada"!!!
To clarify my earlier comment- CDK12 is required for the BRCA1 protein to be expressed. So when cells are treated with a CDK12 inhibitor, the BRCA1 protein is no longer expressed. As a result, cancer cells that have normal BRCA1 gene become deficient in BRCA1 protein and behave like the BRCA-mutant cancer cells, and can be killed by PARP1 inhibitor drugs, like Olaparib. So, the idea is that the CDK12 inhibitors coming up through the system might be able to be used in combination with PARP1 inhibitors on all types of cancers (not just on the BRCA-mutant cancers, which is how the PARP inhibitors are used today). Therefore in principle all of us might benefit from a PARP1 inhibitor, in combination with a CDK12 inhibitor.But that is not for today, a CDK12 inhibitor would need to get through a clinical trial first as monotherapy before we can even see what the side effects are, its a long, slow, expensive system.
Still it is encouraging that there are lots of other drugs being tested as we go along that have not been in the news much- like BET inhibitors, HDAC inhibitors and immunotherapy. And Alpelisib, if we can even tolerate taking the drug. In preclinical studies, Alpelisib works way better when put in combination with Alisertib (Aurora A kinase inhibitor), so maybe eventually there will be a combination trial using lower doses of each drug, with better results and less toxicity?
Here is a link explaining why we need a trial combining Alpelisib with Alisertib:
https://breastcancer-news.com/2018/06/29/aurora-ki...
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Bubblebeard....zero, nothing when I took my first dose, or in fact, throughout that month (other than dropping blood counts, which is expected). On my 23rd cycle at 125mg and have had few side effects at all, other than some fatigue. Good luck, my friend!
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