Ribociclib/Kisqali with Letrozole - Any one on this combo?
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well said Kanga , I’m too new with this still and not good with words.
Toril : I’ve told everybody but I think because I still have hair and middle aged boobs , people treat me no different. There’s the initial “omg” but a bit later it was already yesterday’s news.
Take care all
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Hi Toril and all my friends,
Like Kanga, my hair started falling out after about 2 months after I started on ribociclib/letrozole But it never completely fell out and is just really thin now. My hairdresser gave me some shampoo that thickens hair but to be honest I don’t think it was effective. I hope yours doesn’t completely go and just becomes fine as well. It will be 3 years in June that I’ve been on this combo. I also have extensive bony Mets and they have been stable all this time, so I feel optimistic for you. I have only just stopped work - at 60 years of age it was time and I was feeling so tired all the time. As it turns out it was perfect timing as we went into lock down about a month after that.
After my diagnosis I told everyone and initially it was just like Forza and there was lots of attention, cards, meals and flowers but it settled and life went on as usual. But I liked them knowing because some days I would not be myself (eg distracted or tired and grumpy). But that is your decision on how and when to share your news.
I love the empathy and understanding of this group and reading the tips and advice is great. And the humour. Just hearing how everyone is going is so good too as I feel like I’m not alone. Neither are you - we are all here for you to offload or ask for advice or to tell us where you’re at.
How is everyone coping with isolation. I just have Telehealth appointments and my meds are couriered out to me. The community nurse comes with my monthly Denosumab injection. My family do the shopping so I only leave the house for walks with my dog. I have lots of zoom meetings with friends. We are allowed to travel as far as 50 kms from our home this weekend so we will go for a picnic I think
Goodness! I don’t post often but when I do I can’t stop. Sorry.
Love to all. Stay safe and well
Annie
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Hellou, I am posting interesting paper about CDK 4-6 inhibitors.
I have tried to attach whole pdf file, but I cant. I have it, in case you are interested I can send it to you may by by internal post or an email.Send toNat Rev Immunol. 2020 Apr 28. doi: 10.1038/s41577-020-0300-y. [Epub ahead of print]
Immunomodulation by anticancer cell cycle inhibitors.Petroni G1, Formenti SC1,2, Chen-Kiang S2,3, Galluzzi L4,5,6,7,8.
Author information AbstractCell cycle proteins that are often dysregulated in malignant cells, such as cyclin-dependent kinase 4 (CDK4) and CDK6, have attracted considerable interest as potential targets for cancer therapy. In this context, multiple inhibitors of CDK4 and CDK6 have been developed, including three small molecules (palbociclib, abemaciclib and ribociclib) that are currently approved for the treatment of patients with breast cancer and are being extensively tested in individuals with other solid and haematological malignancies. Accumulating preclinical and clinical evidence indicates that the anticancer activity of CDK4/CDK6 inhibitors results not only from their ability to block the cell cycle in malignant cells but also from a range of immunostimulatory effects. In this Review, we discuss the ability of anticancer cell cycle inhibitors to modulate various immune functions in support of effective antitumour immunity.
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Thanks for the paper Maaaki👍
Quite technical, but the immunostimulatory effects may explain why some immuno suppressed people don’t suffer such severe effects from #codvid19 - I really hope they discover why CDK4/CDK6 inhibitors stop working and what the next step is when it fails for us.
BrisVegas, I’m in Adelaide where we have had 14 days without any new codvid19 cases, so am hoping things begin to return to “normal” but I still wear my mask when I need to go out. I despair for people living in the US with so many mixed messages about what is or isn’t opening and the rising cases and death toll. We are going into winter here, so have had our flu shots but I think because we haven’t got international travellers coming in and out, this may not be so severe this year.
Stay safe everyone💕
Jackie
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haha Annie , nobody gave me flowers or meals though. Like you said , I just wanted it known just in case. I’m not the easiest of people though so the “you look tired , can’t you sleep because of corona” I say “no, it’s the cancer drugs”.
Nearly broke the scanner today 😄 Wasn’t my fault though. The plates that keep you in a cozy place were too upright so when the scanner turned round me one plate was bending and bending and bending ... I thought it would snap and cut me in half so I kept waving but nobody saw that for quite some time. Results next week. Nuclear medicine working at a 60% capacity right now to spread out patients more. Actually is a lot more patient friendly this way.
1 year ago they discovered the lump in my breast ... a couple of days later they found the bone mets in that exact same sketchy scanner I was in today. And 11 boxes of Kisqali later. How time flies.
Take care everybody , always good to see new posts
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Killing 'sleeper cells' may enhance breast cancer therapy
- Date:
- May 7, 2020
- Source:
- Walter and Eliza Hall Institute
- Summary:
- The anti-cancer medicine venetoclax could improve the current therapy for estrogen receptor-positive (ER+) breast cancer, according to preclinical studies. The promising preclinical results for this 'triple therapy' have underpinned a phase 1 clinical trial in Melbourne, Australia, that is combining venetoclax with hormone therapy and CDK4/6 inhibitors in patients with ER+ breast cancer.
- Share:
The anti-cancer medicine venetoclax could improve the current therapy for estrogen receptor-positive (ER+) breast cancer -- the most common form of breast cancer in Australia -- according to preclinical studies led by Walter and Eliza Hall Institute researchers.
advertisementThe research team showed that venetoclax could kill breast cancer cells that had been 'put to sleep' by a drug that blocks cell division (called a CDK4/6 inhibitor), which is currently used in combination with hormone therapies to treat ER+ breast cancer. The research, which used breast cancer cells taken from patients, was the first to show that venetoclax could kill sleeping, or 'senescent', cancer cells.
The promising preclinical results for this 'triple therapy' have underpinned a phase 1 clinical trial in Melbourne that is combining venetoclax with hormone therapy and CDK4/6 inhibitors in patients with ER+ breast cancer.
Dr James Whittle, Professor Geoff Lindeman and Professor Jane Visvader led the research, which was published in Clinical Cancer Research.
At a glance
- ER+ breast cancers are currently treated with a combination of a hormone therapy plus a CDK4/6 inhibitor drug. These force the cancer cells into a 'sleeping' state but do not kill them, leading to a high risk of eventual cancer relapse.
- Using hormone receptor-positive breast cancer samples taken from patients, our researchers showed that adding the anti-cancer drug venetoclax to the hormone therapy/CDK4/6 inhibitor combination could kill the 'sleeping cells' -- potentially prolonging the cancer's response to therapy.
- The potential new 'triple therapy' for hormone receptor-positive breast cancer is now being assessed in a phase 1 clinical trial in Melbourne.
Killing sleeping cells
Around 70 per cent of breast cancer cases in Australia are estrogen-receptor positive, meaning they will grow in response to the female hormone estrogen. The current 'gold standard' therapy for treating these breast cancers on relapse is a combination of anti-hormone therapy -- which prevents estrogen signalling -- plus a medicine called a CDK4/6 inhibitor that blocks cell division, said Dr James Whittle, a clinician PhD student at the Institute and a medical oncologist at the Peter MacCallum Cancer Centre.
advertisement"This current therapy works well in slowing cancer growth, but it does not actually kill the cancer cells -- it just sends them into a sleeping or dormant state, called senescence," he said. "This unfortunately means cancer relapse is virtually inevitable. In fact, the majority of breast cancer deaths in Australia are from patients with ER+ breast cancer.
"If we could find a way to kill these sleeping cancer cells, we might be able to help patients live longer. To do this, we looked to medicines that directly block the proteins that help cancer cells to survive," he said.
The team examined whether ER+ breast cancer cells were sensitive to venetoclax, an anti-cancer medicine that inhibits the cell survival protein BCL-2. Venetoclax is in clinical use for treating certain types of blood cancers, and in clinical trials for a range of cancers including breast cancer.
"We discovered that venetoclax could indeed kill ER+ breast cancer cells that had been treated with a CDK4/6 inhibitor -- even those that were senescent. This was an exciting result as it was the first time that venetoclax has been shown to kill senescent cells," Dr Whittle said.
Triple therapy threat for tumours
In several laboratory models, including those using ER+ breast cancer samples from patients, the researchers showed that adding venetoclax to the combination of hormone therapy and a CDK4/6 inhibitor led to a better and longer-term response of the tumour to the therapy, said Professor Lindeman, who is a clinician-scientist at the Institute and a medical oncologist at the Peter MacCallum Cancer Centre.
advertisement"These promising results provided a justification for starting clinical trials to look at a 'triple therapy' combining venetoclax, hormone therapy and a CDK4/6 inhibitor in patients with ER+ breast cancer," Professor Lindeman said.
"We have initiated the phase 1 PALVEN trial which will, in the first place, look at whether this triple therapy is safe for patients, and will also consider how patients' tumours respond to the triple therapy.
"It would be wonderful to see a new therapy that improves the outcomes of patients with ER+ breast cancer," Professor Lindeman said.
Story Source:
Materials provided by Walter and Eliza Hall Institute. Note: Content may be edited for style and length.
Journal Reference:
- James R Whittle, François Vaillant, Elliot Surgenor, Antonia N Policheni, Goknur Giner, Bianca D Capaldo, Huei-Rong Chen, He K Liu, Johanna F Dekkers, Norman Sachs, Hans Clevers, Andrew Fellowes, Thomas Green, Huiling Xu, Stephen B. Fox, Marco J Herold, Gordon K Smyth, Daniel H. D. Gray, Jane E Visvader, Geoffrey J Lindeman. Dual targeting of CDK4/6 and BCL2 pathways augments tumor response in estrogen receptor positive breast cancer. Clinical Cancer Research, 2020; clincanres.1872.2019 DOI: 10.1158/1078-0432.CCR-19-1872
Cite This Page:
I found this interesting Mandy
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wow Mandy. Great read.
I'm from Melb Aust and attend Peter Mac. My onc is a professor there also but hasn't mentioned this trial to me. I will discuss this with her as it would be interesting to know what her thoughts are on this.
My next telehealth appt is on 24th may so I will let you all know.
Good luck with the results Forza! Glad you're here telling us your story and didn't get snapped in half😉
My latest results were tumor marks almost in the normal range. Midway through my 17th box of magic pills😁
Stay safe everyone
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Interesting about the sleeping vs killed cells ... they don’t tell us anything here and this forum is the only one I look at.
I like the idea of that 3 part treatment , we need more time because I feel this corona is stealing even more precious time from us.
On the sketchy scanner : apparently it’s happened before 😳😳 The radiologist said I should go in said scanner without the scoops / plates because I’m thin enough to not spill over the sides ... Nobody ever called me thin (because I’m not) and we can blush now with these masks on 😂😂😂
*still weird that my markers have always been normal
*the 4weekly xgeva gives me no extra side effects
*remedies for hot flashes ??? Summer is coming ... and I was a winterperson even before the c
have a great weekend ^^
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Phew!
My CT scan today was stable, so I’ll take that as NEAD 🤗
See my onc next Monday to get my blood results.
I’m going to have a nice glass of🍷tonight and relax,
Cheers all
Jackie.
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Congratulations Jackie.
My scan from last month was stable too 🍾
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Great news Jackie - good to know the combo is working. Take care everyone as we come out of the lock down. I still won’t ravel far from home I don’t think
Annie xxx
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!!! congrats operahouse and Kanga !!! I’m joining in.
My nuclear bonescan was also “stable”. That stubborn last little bit of bone met is staying put. But “stable” , very happy. It’s my first year cancer anniversary. Just started box 12 of K.
My lung scan was normal. They rotate here. In 3 months im having a liver ultrasound again and yes another nuclear bone scan. No pet because of my allergy to the dye.
We are out of lockdown here so no time to waste on doctors so I just stuck that zoladex in my tummy myself. Not sure where exactly that implant went. That big needle doesn’t glide in as easy as I’d have liked. And then I clearly was at the point of no return. Will see in the morning. Never boring in my house. All self-inflicted.
Look after yourselves ^^ Jen
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So good to hear you are stable Jen!
I had a phone appointment with my oncologist yesterday who told me my bloods are all good, so I’m happy too. We have not had any new cases of covid19 in Adelaide for 12 days now, so she said it was ok to go out shopping without my mask, and to catch up with family and friends. I think I will still social distance for a while and see how things continue.
I have been home so much my dog is starting to think she is a human. Here she is helping me in the kitchen!Hope you are all keeping well, Jackie
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haha Jackie ... poor pets suffer with owners being home all day long. Can't take care of their secret important dog or cat business. Great news that covid is on it's way out. Hopefully it stays away , time is too precious. I'm taking a cautious approach too. I'm seeing my parents Sunday after 2,5 months ?
Masks are mandatory on public transport. So been sewing.One day I will convince any doctor here to use a phone. I guess they can't bill national healthcare then.
Tomorrow XGeva. I'd stick that one in myself too , seems an easy one , but I don't have needles. For some stupid reason they are packaged 4 in a box but without needles.
I'm not that much of a rebel , I just like to be self sufficient because hopefully I'm moving in 4 months (my offer on a house is accepted 🥳🥳🥳🥳🥳).and I don't want to hunt down doctors straightaway in not my native language.
Stay alert x
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A small study out of Columbia University Irving Medical Center (CUIMC) shows encouraging recovery results among patients with breast cancer who contracted coronavirus disease 2019 (COVID-19), which was confirmed by reverse transcription-polymerase chain reaction (81%) and/or high clinical symptoms (15%) or radiographic imaging (4%) suspicion, most (52%) as outpatients.
Between March 10 and April 29, 2020, demographic, treatment, and outcome data on 27 (0.6%) patients with stage I to IV breast cancer—the majority of whom (19%) had stage I to III disease—were gathered from among the 4515 patients in CUIMC at that time being treated for COVID-19. Of these patients with breast cancer, 96% were female, and the majority were white (56%), Hispanic (44%), or black (22%). Their median age was 56 years (range, 32-87), the median body mass index was 28.5 kg/m2 (range, 21-47), and more than a quarter (26%) were current or former smokers.
At least 20% of the patients with breast cancer had 1 comorbidity; the most common were hypertension (56%) and diabetes and pulmonary disease (22% each). These patients also had undergone treatment in the 6 months before their COVID-19 diagnosis, which consisted of the following:- Chemotherapy, 59%
- Hormone therapy, 44%
- Human epidermal growth factor receptor 2 (HER2)-directed therapy, 22%
- Breast surgery, 22%
- Radiation therapy, 7%
- Checkpoint-inhibitor therapy, 4%
The therapies dropped, however, when it came to the last treatment received before the COVID-19 diagnosis:- Chemotherapy, 52%, a median of 12 days (range, 7-749)
- Hormone therapy, 37%, a median of 1 day (range, 1-81)
- HER2-directed therapy, 11%, a median of 21 days (range, 20-34)
Thirty percent of the patients had at least 4 symptoms of COVID-19 at diagnosis, 26% had 3 symptoms, 26% had 2 symptoms, 15% had 1 symptom, and 4% were asymptomatic. Ranging from most to least common, these symptoms were cough (70%), fever and shortness of breath (52% each), fatigue (30%), diarrhea (22%), myalgia (19%), headache (11%), and sore throat, anosmia, and nasal congestion (7% each).
Overall, just 26% of the 27 patients with breast cancer had to be hospitalized after the COVID-19 diagnosis, and all were discharged alive. They all also were able to receive treatment for their cancer during their hospitalization, either chemotherapy (28.6%) or hormone therapy (71.4%). Intubation was not required for any of the patients needing supplemental oxygen, despite 3 being former smokers.
Following discharge, and after a median follow-up from diagnosis of 26 days (range, 1-38) the only male patient in the study died. The authors view this last finding to be especially important because "COVID-19–positive males have reported worse outcomes than females."
They also noted that due to their small study population, ongoing and larger studies are needed to confirm their results. Especially in light of the fact that 74% experienced some form of disruption in their cancer treatment and "it is unknown whether this represents a deviation from other patients who develop infections on therapy."0 -
Hi: I'm visiting from an Ibrance thread. I was wondering if there is anyone who went on Kisgali after progression on Ibrance? I'm still on Ibrance/Letrozole but wondering about in the future. Would appreciate any info on the difference before I see my MO in three weeks.
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Welp, ladies, it looks like I have progression after 7 rounds of Kisqali/Fulvestrant. Bummer.
Scans will be scheduled for this week (hopefully) or early next to be sure, but the tumor markers are trending up. I have the FGFR1 amplification (not a good one to have) which makes me resistant to CDK 4/6 so that I progressed after only 7 rounds is not a surprise. I'm not happy about it, but at least I wasn't broadsided. Kisqali has been so easy for me, it's allowed me to push the cancer to the back of my mind. I'm afraid whatever comes next (likely Afinitor) will keep it front and center. Blah. I like living in denial.
Anyway, I'll update when the scans come back.
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Oh Lauren, so sad to hear this! None of us know when this treatment will fail us and we have to move on to the next 😞
There are so many treatments out there, and new ones on the way, that I’m sure your oncologist will find the right one for you. Please let us know what they suggest. Was Kisqali your first line of treatment? If so, I think you will have lots of options.
Gentle hugs,
Jackie.
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Thank you, Jackie.
We had discussed Afinitor as a likely next step, but I’ll know more after scan results. If it’s widespread, we will probably go for a stronger chemo. I don’t think it is, but the scans will tell the tale. I’ll definitely update in this thread too.
Kisqali was my first line after metastasis. I had been on Tamoxifen and anastrozole before.
It is what it is but... I’m trying to get over my bitterness that covid may have taken the best of the rest of my time. I had five trips planned this year -all cancelled. I’m facing nasty side effects and may not be able to go next year.
We shall see.
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Sorry to hear this news Lauren. Good luck with with the scans. I’ll be keeping you in my thoughts and prayers
Annie xx
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Lauren. Sorry to hear about your progression. Always a blow to get that news. You will have lots options for sure. I did Xeloda as my 2nd line treatment. I know there are a mix of opinions, but I actually found it easier that my current Kisqali combo. Although Kisqali has been quite manageable for me, on Xeloda I did not have the normal anti hormonal treatment side effects. I still had a great head of hair, no hot flashes, or joint pain. These are my primary side effects with Kisqali. For some, Xeloda side effects are awful, but for me it was a great option. I was on it for one year. There is a good thread (All About Xeloda) if you want to check it out.
I recently had one small lesion on my lung progress while the rest of me is NEAD. I just competed 5 days of SBRT on the one node and will continue on the Kisqali combo. Hope the radiation worked.
I hope everyone else is doing well. I don’t post often, but I do read all your posts.
Ann
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Thanks Ann & Annie -
Scans are scheduled for today, so hopefully I'll hear from the doctor tomorrow. At the very least, I'll be able to get my report from the imaging center on Saturday (at least that's what they said - the policy is 48 hours but it won't be a full 48 by the time they close. Hopefully I won't get a stickler for details.
) Scanxiety will be in full gear tomorrow, but for now, I'm just trying to breathe through it and somewhat control my chocolate intake. 
xoxo, Lauren
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Good news! The scans show NO signs of disease progression. I'm stable! YAY!
Not sure why my markers are going up - I'm going to try not to think about it until next appointment and just take the good news for now. I haven't had a bone scan in a while (COVID), so I may ask for one of those if they go up again. My markers have been accurate for me, so there's a possibility it's growing but just can't be seen yet.
So looks like I'll be here for a while longer - hopefully a good long while longer!
Thanks for the support ladies. ♥
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Wow Lauren!
Feeling so relieved for you!Stable is happy news 💃🏻💃🏻💃🏻😁
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that's awesome news Lauren👌
Waiting on my scan results this Friday 🤞1 week waiting for them .. I hate that 🙄
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Thanks Kanga! It was definitely not the result I was expecting but I'll take it!
A week??! OMG, I'd go absolutely crazy. Wishing you nothing but good luck and a happy result.
I love when I get CTs because I can get the results in 48 hours, regardless of if my dr has called. PET scans I have to wait for dr, but those are easy to read for big areas anyway. Big black blog in a weird place is bad. I can figure that out lol. MRI I have no clue, but 48 hr wait. And bone scans same as PET, I can see the big stuff, but obviously not the small stuff. But at least knowing the big stuff isn't there makes waiting a bit easier, even if I'm wrong I think I'm right haha.
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Got my results today! Stable with some disease not showing up at all👌
Doing the happy dance 💃
Hope everyone is doing as well as can be x
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WOOHOO!! Excellent news!
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oh my gosh Lauren ! I’m catching up here. Phew. Great news.
And Traii, excellent !
Yes , Covid is definitely stealing our trips away. However European borders have reopened now (some with certain restrictions) and planes have started flying again. I’m not keen to get on a plane any time soon though. Still suffering Covid anxiety.
No news from me. In the middle of box/cycle 13.
Labs showed I had bad kidney function , but they recovered again. Just meant even more bloods. Second time I’ve had that , one of those rare Kisqali side effects.Take care of yourselves ^^
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Hi there. Kind of new to this. Just wanted to thank you and all the ladies for your information. I’m on Letrozole now and will start Kisqali July 3rd. Was nervous but you all have been so helpful that I think I might be able to handle this! So thanks again for your information and for calming my nerves. So glad I found you all!
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