Abemaciclib Verzenio for Stage IV
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Back at you Chico - Taking the time to post what you are experiencing, what your doctor advises you, your thinking on treatment option, helps so many people. I can't thank all the people on this forum that have helped me as there are too many.
And pay attention to Luce. She is one smart and well researched lady.
>Z<
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okay, back to verzenio: still having diarrhea two or three days a week on the reduced dose. it is manageable for me, and i make sure i don't get dehydrated, but it is a bit disappointing since i have been wondering if i would get an even better response with the higher dose. meaning, since i seem to be responding to verzenio (my breathing is much better; i can now ascend a flight of stairs without fear of suffocation and stopping every step or two), i am wondering if i could maximize that response with a higher dose, while i am still responding. (the duration of response has been shown to be shorter in monotherapy.) i think this is one of those no-one-knows scenarios.
i also need to call lily and see if any supplements and herbs are contraindicated. (if they even know. not really getting my hopes up. will report back) i think curcumin might be. i would like to start up my self-designed supplement regimen again that i completely abandoned seven months ago so as to not possibly interfere with other treatments, this included. but there must have been something about my diet or the supplements i was taking that slowed progression from when i had the original tumor and between being diagnosed with the recurrence, at which point i gave up on most of the supplements and relaxed my diet, and threw out all my painstakingly-researched notes, thousands of hours of research, in frustration, because i decided that since i had recurred, my diet, etc., had failed me. thing is, i had another CT scan 10 months later, and the cancer had spread to many more organs and bones by then. there is one other possible reason for that: i had had a pleurodesis shortly after the recurrence, and we now know (from a very solid MIT study. yes, on mice, but there is no reason to believe that the same mechanism isn't at work in people. better safe than sorry!) that surgery without NSAIDs before and after can spread cancer, through the inflammation/healing process (angiogenesis and such, which is both important for healing tissue and cancer metastasis). and pleurodesis is all about causing inflammation, in order to be successful. i would encourage anyone with cancer who is getting any kind of surgery to insist on an NSAIDs protocol (and maybe add modified citrus pectin, even though all the studies are by its inventor) before and after, even though your surgeons may be very resistant to that because of bleeding. bleeding is manageable though; metastatic cancer (or more extensive mets), less so.
tbc
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i am still undecided on adding keytruda to verzenio (as done in the JPCE trial) but am tending towards not doing it. i have read about severe autoimmune side effects (including pituitary failure, thyroid failure, uveitis) in a large percentage of patients, and breast-cancer successes only from people with TNBC, so far. and while thyroid failure and-replacement may not soudn like a big deal if we get a longer life out of it, it actually can be a big deal: it can take 6-12 weeks for the synthetic thyroid hormines to kick in, and any needed dose-adjustment can take that long again, and one won't necessarily have a great quality of life for some of that time. and some people do not respond well to thyroid hormone replacement. and then there's the very complicated issue of T4 and T3 (both natural and synthetic) and how they might impact cancer proliferation.
but here's something to know if you are considering immunotherapy: it appears that success rates with immunotherapy are much lower in patients who are (or were recently) on antibiotics. that is important to know, since with any surgery, we get IV antibiotics. pre- and probiotics may help, but please research that well beforehand to set yourself up for success.
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I will be starting Verzenio with Faslodex tomorrow. I'm so glad this thread is here- very helpful. I will pick up Imodium to take with it ( doc suggests cutting one in half and taking it with each dose) and hopefully it will help.
Crossing my fingers that I will get a good run on this combo.
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Sandilee, don't forget to make sure you get blood work for your liver every 2 weeks for the first two months.
Good luck and keep on keeping on.
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Thanks, Celebrate Life- yes, I am schedule for blood work every two weeks and port flushes and Faslodex and more doc visits. My medical calendar feels very full.
I am starting the Verzenio at a lowered dose of 100 msg twice a day. I hope this will minimize side effects and lowered blood counts.
Luce, are you still taking Verzenio? Is there anyone else on this thread that is still on the drug? I'd love to hear from someone who has taken it successfully for awhile, with good results.
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yes, i am still taking verzenio, as monotherapy. have been for five months. it took 3.5 months to feel better, although my tumor markers show that i responded immediately. i had been very close to death when i started it, though, and will be very close to death again very soon once it stops working for me. i am considering giving the 200mg monotherapy standard dose a try again, in order to maximize the benefits while i am responding. i had grade-4 diarrhea on the original dose, though, and wasn't doing well with loperamide (it is a weak opiate and was making me unbearably sleepy). while i still have diarrhea (grade 2 or 3) two to three days a week on the reduced dose i have been on for four months, maybe i'd be okay on 200 mg now, and/or do better with loperamide, since i am definitely stronger and in better overall condition than i was when i first started verzenio.
i have no other side effects other than diarrhea. for a bit, my nails (both finger and toe) started peeling away from the nailbeds, but that has pretty much resolved. they are just a bit fragile (bend easily) now. my hair was shedding more for a while, too, but seems to be doing okay now. not that i really care or check: i have a super-short pixie-cut and don't spend a lot of time in front of the mirror, and zero time styling my hair.
now, diarrhea can really be a problem since it leads to dehydration, and dehydration elevates histamine (via mast cells), and histamine makes blood vessels more permeable and also can lead to an angiogenic response, which is favorable for cancer invasion and metastasis. so try not to get dehydrated.
other than that, i think this medication is amazingly easy to tolerate. i dread the day when i'll stop responding and either have no (good) options or have to move onto something less tolerable. i guess it's all relative, though: some women have strongly complained about fatigue and such. sure, i am fatigued, but i was practically dead before, so fatigue seems a small price to pay. i am still too disabled overall to live what could be considered an active life (for example, i am housebound for the most part, due to weakness and breathing issues), but thanks to verzenio, i am at least not actively dying right now.
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Thanks for your detailed response, Luce! I can see that it takes time to work out the diarrhea issues when they come, but if that can be controlled with diet and medication ( I don't have an issue with imodium in small doses) then that's not too bad. I worry about neutrophil counts a bit, but hope the reduced dose I'm taking with the Faslodex will keep that from being a problem. I had a successful run with Faslodex for over 3 years from 2011-2014, so I'm hoping to get a decent response as my tumors are still very HR+. Fas agrees with my system, but the AIs were very unpleasant. And they didn't work, either. Xeloda and Doxil worked very well for over a year each, but Navelbine did nada. I was diagnosed stage 4 since 2011, but I was probably there all along, but they didn't see it until symptoms showed up.
It's hard work, this staying alive.
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Sandilee, I have been on a clinical trial with Faslodex and Verzenio since January 2017. My dosage was lowered to 100 mg twice a day from the original dose. i also get Xgeva shots bi-monthly. I have had 100% response to my liver mets on this regimen. They have totally disappeared. This happened in late 2017. I occasionally have diarrhea, but find it is easily controlled with Imodium. I find this drug very tolerable. I have experienced side effects such as changes in taste, loss of appetite, weight loss, some hair thinning. I find I get tired easily, but i also try to stay as active as possible. We went on a 10 day cruise in January, and this regimen did not interfere with my being able to enjoy every minute of it. We are off on a 7 day cruise to Bermuda on Sunday, and I don't anticpate any issues with taking Verzenio during that time. Verzenio is definitely easy for me to tolerate. As I have said to others who are anticipating starting Verzenio, don't be afraid of this drug. Hope this helps. Feel free to PM me any time with any questions or concerns. Good luck!
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mzr119--You made my day! That is a terrific response and wonderful news! And like me, you have already been on Faslodex once, and it's still working for you! I see you are Her2+. Are you also taking Herceptin? Apparently the lower dose of 100mgs is adequate. My doc is starting me out on that instead of the 150.
This is very encouraging and inspires me to power through whatever side effects I may have. Thank you so much for sharing.
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cure-ious: are you privy to or finding any updates on the JCPE trial from the presentation at asco? i am not seeing anything other than what you already shared about response rate. i am interested in side-effects, and also whether they distinguished between ductal and lobular and if one got a better response than the other? and if we are actually seeing anything in terms of response that may be due to keytruda or the combo, not just abemaciclib?
thanks for any insights!
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also, has anyone asked constantine for his take on this combo? or on what supplements/herbs/foods should be avoided? the lily pharmacist was clueless. just the standard "no grapefruit" reply. that would include everything else metabolized via CYP3A, i am guessing. but what about antioxidants? some women in the FB group claim no antioxidants, accroding to their oncs. i don't understand what the connection is. that antioxidants protect cells from damage by verzenio, including cancer cells? anyway, if anyone has any somewhat-educated insights or guesses, i would welcome those. it seems ibrance has some kind of list of no no's; i should probably check it out. i have heard curcumin (prob because of the above-mentioned pathway) and chamomile and such.
also, might i get a more dramatic response on a higher dose, seeing that i am responding? i want as good a response as i can get during my response window, so am guessing i could maximize it by going back up to 200 mg. dose that make sense? i heard something about ibrance being "just as good" at 75mg as it is at, say, 125. but what is the science behind that? since cdk 4/6 inhibitors directly interfere with cell formation (tumor and other cells), you would think more would be better, especially in a high tumor load like mine, right? or do i have a blind spot somewhere?
(i love drugbank.ca database. it mentions curcumin, as expected.)
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Sandilee,
I have to adjust my profile. I have not been on Faslodex before. This is the first and only time. I am not taking Herceptin. Just wanted to make that clearer.
Marie
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Thanks, mzr119. I guess I jumped to that conclusion, but I see that it was just a list of hormonals taken.
Well, I'll be the first for the "second time around" on Faslodex on this site. We'll see how it goes. I'm hopeful.
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Hi Luce,
Unfortunately its only that marginally updated abstract: http://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15...
response rate is only 14.3% at the 6mos interval (28 patients), but these people will have already had 1-2 chemotherapy regiments in metastatic setting so maybe that is not unusual, and efficacy still is pending. No side effects in the combo any worse than the individual drugs. It's been going about a year and a half, will have been two years in Nov. 2018.
The overall response rate for this trial must go higher, because the ORR for Abemaciclib alone was 27% in phase 1, unless you think Keytruda is going to somehow reduce the number of responders...
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cure-ious: thanks! i wonder if any of the women in this trial are lobular, and what their percentage of the responders are. there is one trial with keytruda as monotherapy in HR+ cancer, and two of the three responders (only partial, of course; i have not heard of anyone who wasn't TN and had a full response) were lobular. (i am lobular and ductal, or just lobular. i am trying to determine which.). i am also wondering if they are looking at tissue to see if these responses are due to verzenio only, or can in any way be ascribed to keytruda. i doubt they are. i think that response rate at this point may be lower than verzenio monotherapy, which eventually was 17.5% as monotherapy, although i would need to look at the trial and am too tired to do that now. (worked all day.)
if the side effects weren't worse than verzenio alone, i'd go for it, but the worst ones are no worse than keytruda alone, and those can be pretty bad.
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Hi Luce, I do understand the Keytruda risks, but they seem to be getting better about being pretty aggressive at reversing it with steroids at any sign of trouble, patients have to be extremely careful with any fever or sign of incipient sepsis etc. If you think the lobular gives you a better chance, its got to be tempting to add Keytruda if you think you are already responding to the Abemaciclib. I'm sure the trial is following all of these parameters about the MBC subtype and genetics, etc, but they never report them till the very late published updates on the trials, you probably will not even find out that information from expect the initial reports, whenever they do report that.
However, I have heard plenty of stories about how the people who head up clinical trials make themselves generally pretty accessible to patients, by email or phone, if contacted directly. And you have a good excuse that you re in another country so can't just jump into the trial- maybe you should try calling the trial nurse and just talk to them about what they are seeing, what they'd suggest?
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cure-ious: good idea, thanks. i had wanted to do that before regarding side effects they are seeing (although i had read that no potentiated side effects), but the possible lobular advantage i only discovered a day or two ago. so, better question/s now.
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someone on the FB group posted her diarrhea remedies: psyllium husks (i would take those at least 2 hours away from verzenio, in order to not potentially interfere with absorption) to slow down motility and to absorb/hold fluid, and a chinese remedy, huang lian su (recommended by her oncologist-approved acupuncturist) that stopped her diarrhea symptoms within a day or two. sure, there is a risk that taking any substance may interfere with verzenio's workings, but frankly, that risk is there with immodium and everything/anything else you may be ingesting (food, OTC meds, etc.) also. (i personally stay away from opioids, even weak ones like immodium.) logically, i don't see how psyllium would be a problem if taken away from the actual medication, and not used in excessive amounts. i would think it much safer than pepto, with all its crazy food colorings and antacid effect. (i personally like my stomach acids, and what they do.)
huang lian su i more of a wild card. i was taking almost exclusively herbs and supplements (and berberine at times, which seems to be the main constituent in huang lian su, at cursory glance ) before verzenio but stopped them to give verzenio the best chance of working. now i am thinking of introducing some again (actually, have already), and maybe trying to go back up to full-dose verzenio (to get its maximum effects within what remains of my response window) , in which case diarrhea might worsen again. so i am taking a serious look at those two recommendations, and shall inquire with all the naturopathic oncologists i have had about them. not that i expect any definitive answers; this all falls pretty much under " no one knows for sure," just like most matters verzenio (or MBC) -related.
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cure-ious: we misread the abstract from the 24-week presentation of the JPCE trial:
Initial ORR was 14.3%. Patient PD-L1 status by IHC staining (positive ≥1%; negative < 1%), efficacy, and safety data from the 24-week analysis will be presented.
WAS, meaning at 16 weeks. at 24 weeks, it was 28.6
i am still no closer to actually taking it. my oncologists say that, no, the endocrine side-effects are NOT reversible, in most cases, not even with aggressive steroids. sure, pneumonitis and uveitis and other inflammatory auto-immune responses in tissues that do not produce hormones are reversible now, if caught early enough and treated aggressively, but once you have a gland going into failure, that's pretty much it, according to them.
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Dang, girl!!! Where'd you find that poster?!! I LOVE it!! I will study it tomorrow, thanks so much, I am much more uplifted to see the ORR jump, even though I don't even know if its better than what they were getting with Abemaciclib alone in the first trial..
All I know about the keytruda problems was the situation Barbara Bigelow described in her blog, she went into sepsis as a result of being on some combo trial for TNBC (had mutated from ER-positive and it took awhile for them to realize it). She nearly died and you are right, it fried her adrenals for good, but she did survive, the cancer seems to have completely disappeared and she's one of those "maybe cured" patients" :
Her blog https://barbigwire.com/
read the blog entries from around March to Nov 2016 to see her describe the experience
I've been following her blog from the beginning, since she was diagnosed right before I was...
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Aack!!
The poster Luce provided for the JPCE trial showed exciting preliminary results that adding Keytruda to Abemaciclib just about doubles the response rate at six months, same as it did earlier. And also great that the response did not correlate with PDL-1 levels, which right no the only way we can get access to Keytruda is if we overexpress PDL-1, which few will. But very few patients tested overall (started with 25, now down to 8 at 6 months). So its very preliminary but the first time any immunotherapy hints for benefit for ER-positive MBC!
But now they are moving to a different protocol, where Abemaciclib will be combined with Keytruda and Exemestane (AI), and for this trial nobody who can have had prior CDK4,6 inhibitor, or chemo, etc. So, it looks like they are headed to see if this now can be a new preferred firstline choice for future patients. And what about us, we are being left behind?! Where do we go to sign up for our Faslodex- Ibrance-Keytruda trial?!!!!
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cure-ious: i got the poster from one of my oncologists who had attended ASCO.
yes, the finding that PDL-1 overexpression's not needed is great!
still, i am not ready for the endocrine damage, so won't go on it, at least not for now. although now would probably be the perfect time to get the maximal response; it's been shown that a verzenio lead-in works even better than starting both at the same time.
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luce, thank you so much for that poster! I've been searching online like crazy but it doesn't seem like it's been officially published anywhere. Nearly triple the response rate at 6 months compared to monotherapy (28% vs 10%) is pretty good, especially if it stays or improves as more patients are followed up for longer. I was hoping for some CR's, but maybe that will take more time. The disease control rate (objective response+stable disease) is also really nice, over 80%.
cure-ious, I don't think they'll move away from this protocol. I think the newly announced "part D" in combination with anastrozole is an addition, not a replacement. My guess is that now that the CDK/PDL-1 looks to have achieved proof of concept in the clinic, there will be more trials expanding on what appears to be at least an additive, if not a synergistic effect. The market for hormonal-naive patients is a small fraction of the total ER+ MBC market. The market for CDK-naive patients is also going to be substantially smaller by the time this combination gets approved. Even assuming that economic considerations are the only thing driving the direction of future trials, I can't see Lilly/Merck giving up clearest, juiciest commercial opportunity, which would be patients that have failed one AI plus a CDK inhibitor, possibly also failed faslodex and are now contemplating the unappealing choice between Afinitor/exemestane and cytotoxic chemotherapy. Especially now that we are learning that resistance to CDK's is nowhere nearly as common as resistance to hormonals. While everybody wants to be able to be the frontline therapy, until there is a cure, at any given time there will be more "later line" patients than first line patients, so to ensure a strong launch it would be beneficial for them to have an approval for later lines as well as front line. My guess is that if the current results for the duplex combination hold after longer followup, they will move into a registration trial for the duplex next. The inclusion criteria would be interesting to see, but having a predefined cohort with previous exposure to hormonals and CDK inhibitors would make a load of commercial sense, as these would be the patients they would most easily get at launch. If they don't get those patients, someone else with a CDK inhibitor will (there's already a trial looking at avelumab/ibrance in patients that failed an ibrance/AI regimen, the PACE trial).
I think that these results just open the door, and in the next few years there will be a slew of trials figuring out the best combinations and the most logical sequence of treatments.
Hope burns bright today.
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still, important to remember that the endocrine side effects are both common and irreversible, and tricky to treat. most people take the risk as trade-off for extended life span, but i don't want to live with both endocrine failure and cancer. thyroid hormone replacement takes 6-12 weeks to kick in, and every time it's adjusted. pituitary failure would mean " a lot of shots", according to my oncologist. the adrenals produce a number of hormones that are tricky to replace adequately. the endocrine failure rate will likely go up as the trial progresses.
the "immunologic memory" mentioned is interesting, although i am not sure of how much use that would be while readministering keytruda until the combo fails (or verzenio does, and gets replaced with low-dose chemo, which may work well with keytruda also).
also, very small numbers, and one person died, and no CR so far. my oncologist doesn't really expect CR. he also says that in combination with faslodex (or other endocrine therapy), some women become and stay NED on verzenio (or other cdk4/6 inhibitor) alone for years, without the risks of keytruda's more serious side-effects. something to keep in mind.
the biggest hope for adding keytruda would be a more durable response, especially in verzenio without endocrine therapy. i don't think my oncologists are holding their breath for a full response. but you never know.
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there seems to be some evidence that high intake of antioxidants may protect tumor cells from verzenio.
CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought
https://www.cell.com/cancer-cell/abstract/S1535-61...(18)30128-4
(hit me up for the pdf if you can't unlock this.)
interestingly, i saw the biggest drop in tumor markers during the weeks i was out of melatonin. this is disturbing, since my diet is ultra-high in antioxidants, now that i can eat again, and i am also taking/started taking some supplements that happen to be antioxidants.
just something to be aware of. and if you are more organized than i am, maybe keep a supplements diary and see if it correlates with your markers or imaging.
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Thanks Luce & Piggy, I am very excited to see these hints of efficacy for immunotherapy for ER, in prinicple it should make the treatment last much longer for those who are responders, given that it already iseems to significantly ncreases the odds of a response. , and hopeful that they continue on with the main trial. The poster indicated only eight patients remaining on treatment, but if they are still enrolling that should jump right up. What would be just excellent would be trials large enough so that we get some real numbers comparing time to progession for Abemaciclib with Keytruda, versus a 3 way combo with AI or with Fulvestrant, and long enough and strong enough so the real side effects risks appear too. And, yeah, because what we are looking at otherwise secondline is Faslodex-Ibrance or something with Affinitor, we need something with more punch, more transformative..
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I am excited for this combo. If there is a possibility for durable response I would love it with some of the even nasty SE's. I have younger children and need to get them raised. Right now my QOL is them. My cancer has moved fast so I'm praying for this to ramp up quickly.
Mary
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Cure-ious, I had completely missed the fact that only 8 patients remained on the study combination. That's a bit worrisome, unless the duration of the effect is much longer than the duration of treatment and in real life they could rely on that elusive "immunologic memory" to retreat only if necessary. They show that the the two patients with the best responses (100% reduction in target tumor) are off treatment and the tumors are still stable 25 and 50 weeks later, respectively. It would have been nice to have a more clear indication of WHEN they got of treatment, because that Figure 4 sure doesn't make it easy (can't tell if there are any solid lines that convert to dotted lines at some point). I also wonder what else was going on with those patients that prevented them from being classified as CR (I'm hoping bone mets that might take a while to resolve).
luce, thanks for the sobering summary of the chronic side effects - I'm not up to speed on the long term effects of Keytruda, other than Type 1 diabetes that seemed to pop up in a couple of news stories (not that diabetes isn't scary in and of itself). I was more aware of the nasty acute/sub-acute reactions that people can get that can lead to organ failure but got the impression that they are getting better at recognizing and aggressively treating for those. Still, one person died, as you pointed out, so maybe they are not as good as we would have hoped at dealing with the rogue immune responses.
The side effects would be another reason to believe Keytruda may not be most successful as part of a first-line therapy for MBC. Considering the pretty substantial benefit a majority of ER+ MBC patients get with AI/CDK combos that have reversible, not-deadly and relatively tolerable side effects (for most people, I know that for some the side effects are crippling), I just can't see most women choosing a wild card like Keytruda off the bat unless they can show some sort of spectacular and durable effect that can't be obtained in later lines. Hats off to the treatment-naive ladies that would be willing to take the chance so we could find out.
For me, at this time, the risks would just be too much for what we currently know to be the benefit. I have a 6-year old daughter that I desperately want to see grow up, but right now there's about a 20% chance I'll make it to 10 years with existing treatments, so I don't know that I would take the risk of dying of sepsis or getting severe endocrine failure for an unknown chance of living longer. Now, if the cancer turns aggressive and mets start popping up everywhere and I go through 2-3 treatments in rapid succession, then the equation would change - then the chance of making it to 5-10 years would become much, much smaller, and a 10-20% chance at a durable remission might be worth the ~20% risk of a serious long term side effect and the 5% risk of death. The tipping point of risk-benefit is probably different for each of us.
I don't know if the future of immunotherapy for MBC is a PDL-1 inhibitor and where in the sequence of treatment it would best fit. I think that the most positive thing about this trial is that it appears to confirm the in-vitro findings that CDK inhibitors cause immune infiltration in tumors and can turn "cold" tumors like HR+ breast cancer "hot" and responsive to immunotherapy. Hopefully this will spur a lot of interest into exactly what kind of immunotherapy regimen might be best to take advantage of this finding. Maybe the OX40 treatments that require tumor infiltration by the immune system would work in this type of combination and with much fewer side effects.
Well we be around long enough to find out? I don't know. I want to hope so, for all of us. But even if it takes too long for me to benefit, I'm still hopeful that if my little girl ever has to go through this at some point she will have a much better chance at a life-span that is counted in decades.
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