Overall Survival With Ribociclib Plus Letrozole in Advanced Breast Cancer
The New England Journal of Medicine
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"This report provides data on overall survival (OS) from a phase III trial of ribociclib plus letrozole for the first-line therapy of HR–positive, HER2–negative advanced breast cancer. The findings indicated that median OS was 63.9 months with combination regimen whereas it was 51.4 months with letrozole alone.
This study shows that first-line therapy with ribociclib plus letrozole provides a significant OS benefit versus letrozole alone.
– Neil Majithia, MD"
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Hazelgreen
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P.S. The actual study has open access in the New England Journal of Medicine. It indicates that the subjects were all well-functioning patients who had not received previous systemic endocrine therapy or chemotherapy. The data cutoff date was June 10, 2021, more than sixyears since the last patient was recruited. At that date, 9 % (30 patients) were still receiving ribociclib plus letrozole while 5% (17 patients) were still receiving placebo plus letrozole. Who knows how long these patients may remain on their original treatment!
Although it is always good to know the median overall survival, we should also keep in mind that 50% of the patients survived longer than that number of months, and a few will survive much, much longer.
No data (yet?) on Kisqali as 2nd or 3rd line of Rx? It was approved 5 years ago. I wonder if there are data from patients who have been on it, outside a clinical trial. Is there a tracking system of some kind?
I am in a down mood today; the things that were making me happy are failing (dance program, mostly), Have to find other sources of joy and buoyancy, and deal with disappointment. So with that caveat, I note that the median survival not only tells us that half survived longer, and we do not yet know how long, but also that half survived for less than six years. Does that mean disease progression, or actual survival? With apologies for negative thoughts....
Hello Chris O,I'll see if I can find a "real world" study of Kisqali for any treatment line. You would think the drug companies would keep some sort of tracking system, at least for the results of the various studies.
It does seem that you are in a down mood today! I'm sorry to tell you that "overall survival" means just that - 50% did not survive for 63.9 months (or less). In fact, the study indicated that 8 (2.3 %) patients died during treatment so there are no guarantees even for that initial
period.
However, given your age, race, and place of residence, you are more likely to survive longer than those younger, non-white, and/or not living in North America. I hope that is cheering news for you. Also, spring is on its way!
Right, thanks. Cindy. Spring makes me grumpy! Always has. I like cold and winter. I like hot and summer only if I can swim at will (don't like being stuck inside with air conditioning). The transition is rough. Very strange; since I am a gardener; this should be a happy time of hopeful planting. It is freezing and windy today, and I had a good dance class outside for the first time in a long time, so I am no longer in the dumps. Same info doesn't affect me the same way....but
Sixty months is five years - just what I was told from the beginning - average 5 year survival. And this was the first line of treatment for study participants, so that five years is not on top of years of something else.
And I see below that it is a CDk4 inhibitor. I have already done Ibrance (+Fulvestrant). My oncologist wrote in her notes that the Fulvestrant failed and she took me off Ibrance because it gave me a rash. The latter is not true. It seems that, if there were new lesions when I was on that combo, then both failed. I am on what is more or less the oral version of Fulvestrant, It is working. Makes me wonder if Kisqali might work for me after Ibrance failure. Jumping ahead. Not definitive that i have progression on the oral SERD yet.
As I understand all three are similar “Targeted Therapy Treatments”that are also called CDK 4\6 inhibitors. Ibrance was the first to be released, produced by Pfizer and was given approval in 2015. Novartis released Kisqali in 2017 and Verzenio was brought out that same year a few months later by Eli Lilly.
They are all in the same drug class but as I do more research I’m finding that verzenio and kisqali are superior to ibrance. They are more potent inhibitors of cdk 4 than ibrance. They actually have considerable pharmacological differences. Results of a head to head trial of kisqali vs ibrance should be out sometime in 2022. I have a feeling it’s going to shown that kisqali is superior. I also found an article from Dana Farber that said resistance to a cdk inhibitor may be reversible if you go off of it for 7 weeks and then back on. I’m doing well on ibrance but I have told my oncologist when my current meds fail I would like to circle back to verzenio or kisqali. Although sometimes I wonder if I shouldn’t just make the switch now while I’m doing so well.
I was thinking the same thing. I’ll be starting my 3rd month of Ibrance some say if you have little to no side effects stay on it. But I want something that’s going to really inhibit the cancer from growing. My onc said he would switch me if I wanted. I think I’ll wait for my first set of scans and go from there. Your research was very helpful thank you!!
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Great point, lluvpuppies! I had a similar convo w/ my doc a year or two back....I had asked her for list of my subsequent treatments and Verzenio was on that list (could easily be Kisqali instead, I'm sure...)....We talked specifically about putting a *different* treatment b/w the Ibrance and another CDK inhibitor to allow a break for any "reset" for additional benefit...i.e. wouldn't want to do them back to back and definitely don't want to change while the Ibrance is still doing okay...
Yes, I'll have been on it for seven years next month....but always on the verge of a change (next up = Piqray)...I just wanted to know what the future would bring because I'm a control freak? Honestly, and this will sound bizarre/potentially morose (to me it's not; it's comforting), butI keep a spreadsheet with predictions of my longevity and, to a degree, expected quality of live (e.g. time on oral vs. IV treatment)...So I wanted to research the subsequent treatments to help me at least sketch out my future....better for my mindset and planning/dreaming?
But that's just me, it takes all types, right?
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7 years is an amazing run! I’ve been on ibrance almost 2 years. I too research all the potential meds and med combos and all the new meds on the horizon. Love the idea of spreadsheets lol
Have you made any correlations between exercise and markers or nutrition and markers? I’ve increased the amount of exercise I do.. I workout almost an hour everyday 6 days a week. I also do the care oncology protocol. I do green tea and green powders almost everyday. I’ve gotten my markers into the teens-twenties. So fingers crossed I’ll get a good long run too
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Wow, sister!, yes to all!
The impact of exercise on TM's is substantial, I think...About 2 years ago, I was dealing with a minor bout of progression, and decided to finally exercise *properly* for fighting cancer. This means *exercise hard* based on some great studies out of Sweden....
I posted here at the time....I brought my TM's down like 25-35% within a month or two. It was crazy....
...but do you know what's even crazier? I stopped exercising!!! That's how much I dislike it!! I've said to people..."Oh, you claim to hate exercising but I can top that! I'd rather die of cancer than exercise!! Not sure whether to put a smiley or sad face to that! Maybe a shrug emoji?...
I have a post here.... I think its headline is "I did it", if you want to search my profile...So in desperation I took up exercising and it really made a difference. Then I started the COC protocol and thought to my lazy-assed self (!), why break a sweat when I can just pop some pills? So far, so good, but now that weather is good I do need to resume the workouts...
I also hope you have a good long run...me too!
Best,
Lynn
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Actually, this is a link to the post, including a graphic (!!! Yes, I'm *that* person!), not sure it will work....
And, btw, in a re-read my "I did it!" post and saw that the first month or so showed like 17% decrease in markers...that trend continued a bit to achieve 25% on one, 35% on another....has since increased *alot*. While still technically stable, I've had a couple of/few incidents of "progression", i.e. growth *and* new mets. Have remained on treatment, though.
I don't know - I think it's unknowable for me - if the exercise decreased the markers, or improved the cancer. But I think it's safe to say it's nothing but good...
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Love it! Thanks for the link. That’s pretty incredible actually! You should keep it up! Find something you love.. walks or hikes? Biking? I love my Peleton!I’m an exercise junkie though and for me my workouts are usually a highlight of my day. I may workout even harder now
Interesting too that your oncologist has kept you on the same meds even with mild progression. Makes me wonder if most are too hasty in switching meds?
You’ve given me lots to ponder this evening! Take care
❤️
Mandy
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Hi Mandy! *Most* are too hasty....I've seen it here a hundred times....but I think that's changing? My doc (aka my angel) sensed this right away....I went from one met in Jan of whatever year I was dx'd metastatic, to "too many to count" 11 months later. Nearly any doc would have said "failure" of treatment, change. She said...let's give it a couple of months. I stabilized and remained on that treatment for *years*. She gave me literally years of life, which is why I give her wine, bagels, etc. every time I see her!
Let me know how things go! I’m still on ibrance and my scans have been stableBut my tumor markers have been creeping up. I think if they continue to rise I’m going to switch to kisqali and see if it makes a difference. My onco doesn’t seem to think it will but I’m convinced it’s a better drug than ibrance and would like to switch while a cdk 4/6 is still working.
My onc wanted me on Kisquali from the beginning but my insurance company said no Ibrance. I finally got approved I’ll start the week of the 4th of July
Don't forget that some us have lung damage from these meds! I was on Ibrance for just a few cycles in 2016 and now have permanent damage, Interstitial Lung Disease, and get out of breath very easily. I cannot walk the 100 yards to our mail box without stopping at least once each way and 4 or more each way when it is humid out. I have to see a pulmonologist and am on 2 Rx puffers.
i have not forgotten about the possible severe side effects of Ibrance. i opted not to take Ibrance for that very reason. when i was diagnosed with mbc 4.5 years ago, i did a ton of research and really dug deep. at that time, the additional one year was PFS and not even OS....(although my oncologist was surprised that i had found that out during my research as she certainly wasn't going to tell me. however, she did not disagree with my findings). well, i guess that part has changed a bit according to study above. either way, still isn't enough to convince me. for me, the benefits did not outweigh the risks of side effects. and i had enough IV chemo during my primary BC diagnosis 8 years ago to last a lifetime. i had severe side effects and swore off chemo forever...after i finished. i have heart damage from the red-devil. and severe neuropathy from the taxotere. and i was hospitalized twice during chemo for severe lung infections. so i am supposed to eat healthy but then allow poison into my body. not for me. i have done letrozole only (and Zometa) for the past 4.5 years and still bone-only. i am currently thinking about a change from letrozole to Faslodex as i am hearing that it is a superior estrogen blocker.
so i hear you and i have not forgotten about the potential side effects. i am so sorry. that you are one of the unlucky that ended up with interstitial lung disease. bad enough that you struggle with mbc but now to have your lungs impaired by the treatment is truly sad. my heart goes out to you.
i realize my views are unpopular. and i also know that i am in the minority. but we all have to make what we feel are the best informed decisions for our own body. and those choices can change with time and circumstance. the whole 'quality of life' vs 'quantity' debate. i am sure that Ibrance has been a great drug choice for many. and i also realize that those who are not ER positive have less choices and i appreciate that. just re-iterating that it is a 'choice' based upon informed decisions.
hi Cindy, good to hear of this progress! imagine where we might be if more than only 5% of breast cancer research donations went towards curing MBC and not towards primary BC and early detection. i'm sure many of you are familiar with the non-profit METAVIVOR which is run by those with MBC and working towards change in those percentages. we MBC'ers make up over 30% of the landscape and yet only 5% of research funds allotted. i am not an expert in this at all. it just crossed my mind when i read your post that more research money for MBC would be so appropriate.carole xo
I so agree with you about the need to redirect medical donations away from early breast cancer (which 1 in 8 women get, but kills no one) towards MBC which ultimately kills 1 in 24 women (about 1/3 of those who get early BC). I think a focus on mammograms is enough to alert women regarding the risks of BC, but, for those with early tumours, surgery and adjuvant meds seems to be sufficient in the majority of cases. I really don't understand where the billions of dollars raised through years of pink campaigns have been spent. It seems to me that many of the current breast cancer organizations raise money primarily to keep themselves afloat.
hi Cindy. yes, i did the math too and 1 in 24 sounds pretty accurate.
although sadly, in reality, the numbers of those dying from mbc are probably even higher, depending on what is put on the death certificate by the MD filling out the form. for example, my Mom died from COPD, however her death certificate stated she died from 'malnutrition'. well in the end, yes of course she was malnourished, but the reason for that was the COPD. i have instructed my sister, who is also my power-of-attorney, to make sure my death certificate states that i died from MBC! i want to be counted. now if my mbc spreads to my brain or lungs or wherever, the doc may be inclined to say i died from lung cancer....or maybe malnutrition as well. but my true cause of death will be MBC. i think it is usually your PCP that fills out the death certificate and not your oncologist. or maybe some random MD that is assigned to you if you die in hospital. you get my point. i want 'them' (the statisticians) to know how many are truly dying from this horrible disease.
and yes, i too am confused as to who allocates where the billions of dollars from donations goes where? if left to Big Pharma to decide, then of course they will align with the pink brigade and focus on the primary BC...so that those patients can progress to mbc where the real money making is happening. much more money to be made from our pain, suffering, and desperation with mbc. $15,000 a year for Ibrance alone? seriously??? and after all these years and all these funds, the best they can do is 'one more year' of OS. i know i sound cynical....because i am. (obviously my opinion and my thoughts)
Hi Carole,You do seem to be indeed cynical, but, with North America being so focused on profit (i.e. greed), it is hard not to be. Fortunately, there are many genuinely kind and trustworthy individuals. I try to keep such folk in mind when I contemplate the news, and realize how much suffering there is in this world - while a very few human beings hog much more than their share!
hi again Cindy. i do not disagree that there are many kind, caring and trustworthy people in this world. in fact, most people i know fall into that category. you certainly do!!! and i believe i do too, believe it or not😉. i worked as a nurse in a busy, inner city ER and loved 'hands-on' patient care. and i felt like i made some small difference in people's lives every shift i worked. and so did my amazing co-workers. i miss my career so much! top administration was another story....it was all about the 'bottom line' and how much revenue/profit we could produce. hence, working long hours without a break, short-staffed, and without enough equipment and supplies etc. but we did the best we could. i remained a very dedicated and caring nurse as i had patients who relied on me. yes, defending my honor a bit...lol.
my cynicism is aimed solely at Big Pharma executives. they make a lot of money off of 'us'. and those commercials just kill me. i am sure there are many individual researchers out there who are working so diligently for the 'cure'. but i cannot wrap my head around the fact that only 5% of donated funds are earmarked for MBC. how can that be?? that is where my cynicism lies.
Actually, I find many cynics to be kind people. My guess is that, if we met in person, you would strike me as a kind (and intelligent) soul. You clearly loved your mother, and your inner city patients. Since I worked for 38+ years as a forensic psychologist, I think I might be familiar with personalities similar to those of some of your patients. I met some of the most thoughtful people I ever knew in prison (usually not as staff).
I think "the system" in the USA may breed more greed and corruption than the system in Canada which has a number of socialized benefits (health being one of them), but I guess, that's a long conversation....
Hi Cindy--So that means that OS is 12.5 months longer with Kisqali and Letrozole vs Letrozole alone. Hmmmm. One year. I just saw a new onc that said that fulvestrant was the best estrogen blocker overall. He gave me a recent study of fulvestrant and verzenio. This study only shows PFS--but I have not read the whole thing. It is the MONARCH 2 study done on those that have already progressed on e-therapy. After about 1.5 years the PFS was 16.4 months with fulv plus verzenio, and 9.3 months on fulv. alone. They get us months or maybe a year, which does not seem like very much to me. I agree with Carole, more money to Metavivor. Thanks for posting the study! Kay
Hi LadyKatrina - I noted the same thing...about a year in OS which I took to be *good news* since we've known that these CDK inhibitors add about a year to PFS prior to a need to change but it was for a long time *unknown* if that full year could be added to OS...and it sounds like it can! I understand that this is not true for all treatments, i.e. you might increase PFS on that treatment by X, but in the end, OS increases by only a fraction of that...
**THANK YOU** for sharing this! Answers a question I've had but have not looked into for a long time, I'm so glad the data's available!
I remember reading in Bestbird's book (Bestbird from this site...), An Insider's Guide to MBC, that if you live for 5 years there's a...54%?...likelihood you'll live for *another* 5. I'm taking that one to the bank! :). **But** I acknowledge that this % came from participants who might not hav had access to these CDK inhibitors, so I guess we can't know for sure that both %'s are true at the same time....but I'm going to assume they likely are...
Dear Hazelgreen, thank you for posting this. I am a bit confused though, maybe you can help me, as I am quite new to all the treatment lines available. Does this mean that Overall median survival has increased for those having this as a first line of treatment, then moving on to other treatments or that they survived for this length of time whilst on the Ribocilib plus Letrazole? Sorry if this is a silly question, I have managed to totally confuse myself reading all the threads and need some explanation.
Sadly, all it means is the first option you mentioned. Although a few people (30 or 9 %) were still on the treatment at the end of the study, most had already moved on to other treatments, and the median survival for these people was 63.9 months. However, as Lynn mentioned above, once someone survives cancer for 5 years, they are considered likely to last another 5 years or so.
I didn't report this earlier, but your question prompted me to go back to the 2022 paper in the New England Journal of Medicine: (nejm.org/do/10.1056/NEJMdo0...
The 2022 paper stated, "The median duration of exposure to trial treatment in the ribociclib group was 20.2 months", so most subjects took ribociclib + letrozole for less than two years. "The median duration of exposure to placebo was 14.1 months".
Thanks for your question. Please let me know if anything is still unclear.
Thank you for taking the time to explain. It’s all so overwhelming at times. I am 14 months since MBC diagnosis on Letrazole & Palbocilib. I am just desperate to survive as long as possible as I have 2 beautiful grandchildren aged 2 & 5 months. I am trying to make the most of every day but it is a struggle at times.
I am hoping and praying that this drug combo serves me well and that I will be on it for a good few years yet.
Thanks for your reply! I have no grandkids, but I can well appreciate your joy in your two very little ones. There is nothing like watching the reactions as little ones discover life's pleasures, and the cuddles are heart-warming. (My husband and I had adoptive grandkids from birth to age 4 to 5 before they moved most of a continent away.)
Given that you are in middle age, you may well do well on palbociclib and letrozole for at least a few more years. Most studies seem to indicate that older women last longer on the various medications than younger women.
I think there are now studies in progress indicating that a switch to another targeted drug may also work once there is progression on the first combination. Also, a treatment break apparently may reset the body to respond again to the targeted drug. It is certainly in "Big Pharmacare's" best interests to support further sales so it does not surprise me that these other studies are underway.
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