Susan- so long as you have the PI3K mutation you can respond to the drug. Their data showed those with a p53 mutation did not respond, but they lacked the PI3K mutation.
It;s interesting to reflect on the fact that the trial tried to exclude you twice, once because the cancer also showed some modest Her2 expression, and yet against all odds, it turns out that you are a responder! Ha!! Good call on Dr. Rugo's part..
Don't know what the plan is yet, will find out on Monday. But my trial RN did call me last week & say that she saw within the trial literature that you can stay on the trial without taking alpelisib, so that would leave me on fulvestrant. My MO would have to make a case for me getting a benefit from only one drug. I will post when I find out.
Thank you for all the research that you do, I find it very interesting.
I continued on Fulvestrant (through private coverage as Novartis removed me from the study when I couldn’t tolerate the Alpelesib). Now I have a dilemma. Last CT showed some improvement in my liver and lung spots but recent bone scan showed I now have bone mets as well. I want to stay on Fulvestrant but obviously need to control new mets. One idea is to add on ribociclib. But so far neither Novartis nor my insurance is approving since I was already on Pablo (which seemed to work well for me except for developing a liver met. Do you know if anyone has done Ribo after Pablo?
My oncologist wanted me to take ribo after palbo but it was also denied by ins. Maybe the newer one, verzenio would work? I think it is different enough from the other 2 to warrant trying but my oncologist didn't like the idea. I still may want to try eventually so will gear up for a debate when the time comes.
Sary & HLB, This stuff is so frustrating! The ASCO meeting in June reported that like 90+% of the time that patients progress when on Ibrance-Femara, it is because of new mutations were acquired that allowed the cancer to escape from inhibition by Femara, and those cancers may well remain sensitive to Ibrance! So unless you have specific sequencing showing that mutations have developed that indicate you have developed resistance to Ibrance (such as loss of RB or overexpression of Cyclin E), on average, you are probably still a very good candidate for Ibrance (Or Ribociclib or Verzenio). How to get insurance to pay for that is the problem!! And the CDK4,6 inhibitor doubles the time spent on Faslodex, regardless of whether it is first or second line (or later line). Another reason you want the CDK4.6 inhibitor is that it makes the cancers more sensitive to killing by the immune system (at least in lab models) and I was watching a video where oncologists were saying that the longer people stayed on Ibrance-AI regimens, the more they see continued improvement in bone etc, which is not usually the case with drugs that taper off, the speculated that they might be looking at a constant improvement because of giving the immune system time and opportunity to work on the mets. So its worth pushing to stay on Ibrance et al., especially if it likely helped in the past treatment, and/or alternatively to plan to includ a Verzenio-alone treatment (or in some other Verzenio-drug combo) in a later treatment.
Curious that is very interesting. Ibrance/faslodex was my 3rd treatment and I was on it for 16 months. When verzenio came out I heard how good it was alone on heavily pretreated. oncologist said something about they haven't studied yet to see if it's better than ibrance. I said why even compare the two, they are different enough to consider it a separate tx! Esp after he thought I might benefit from kisquali which is more similar afaik.
Thank you so much for the replies! This is very helpful. I am continuing to appeal the insurance and will also wait and see at next week's CT if the Fulvestrant is still helping liver/lung. If Fulvestrant + Ribo isn't the path, my MO wants me to do Everolimus and Exemestane. This is so confusing!
Hope Rugo tweeted a great animated explanation of the PI3K process from the New England Journal of Medicine. I don't know much about using Twitter but I think if you follow @NEJM or @hoperugo you can watch it. You have to be a paid subscriber to access the cartoon on their website. Helped to explain to me about why my blood sugar is affected by the drug.
Onclive video- (I love Joyce!)
She mentions having a 20 year mets survivor who is currently having a great response to Alpelisib-Faslodex, even after having been on everything including two other faslodex combinations..
Appt with trial RN & MO yesterday. I am still on the alpelisib trial even though I will not be taking alpelisib as even the lowest dose is far too toxic for me. As I mentioned in an earlier post, we thought there was the option of staying on the trial on the single agent of fulvestrant only. I have had 3 doses of fulvestrant now & don't seem to have any noticeable SE's. I will have scans again in 2 weeks to see how things are, fingers crossed for halting the liver met.
Was interviewed for this Healthline video about metastatic breast cancer mentors and if you click on my name at the bottom of the web page, you can read an article I wrote: MBC Mentors
Very informative video! Thanks for sharing.
I had a friend who was a 20+ year MBC survivor. She died last February. In the end, I think she just gave up because she was in a wheelchair living as a shut-in. Her bone problems, ironically, were probably caused from being on bisphosphonates (bone strengtheners) for so long. They had never had someone live so long back then and didn't understand that longterm usage of bisphosphonates would cause osteonecrosis. It wasn't the cancer that killed her.
Hi Susan, thank you so much for sharing. I was also part of a mets support group before moving this past year and I think often about my friends who have now died. It helps drives the advocacy work I try to do.
I really liked your biography "Susan...currently focuses on small, hands-on ways to make the world a better place."
Hi GG - I'm glad the fulvestrant will be still covered by the trial, I hope your scan shows stability/regression.
So the updated info on Alpelisib+Faslodex trial was released today at the SABCS meeting in San Antonio. Numbers look good but I am not the best at interpreting some of these different parameters. PFS was around 11 months for first or second line treatment, as compared to 4-6 months for Faslodex alone. Also they are pushing to get a ctDNA test going with Qiagen and another company because it is a fast and accurate way to gauge response to the drug (imagine if you could just follow it by a blood test rather than whole body scan)
PI3K inhibitors can increase blood glucose levels which in turn decreases the drug's efficacy because of release of insulin. Here's Siddhartha Mukherjee in the NYT on the ketogenic diet "as a form of molecular therapy"
It's Time to Study Whether Eating Particular Diets Can Help Heal Us
By Siddhartha MukherjeeDec. 5, 2018
A few weeks ago, I had a minor surgical procedure — the repair of a congenital abdominal hernia. The operation went well. I returned home with a stash of instructions and medicines. There were clear guidelines for which drugs to take for inflammation or pain, in what dose, and in what order and intervals.
But the surgical wound was slow to heal. And so, while continuing the anti-inflammatory medicines, I added an antibiotic, and began to wonder if I should change my diet to aid the healing process. After all, I was pouring molecules into my body. The antibiotic was designed to fight a type of microbe. The anti-inflammatories worked to reduce inflammation. Why not find a different molecule designed to encourage blood-vessel growth, or boost the division of stem cells in the skin — a molecule delivered not in the form of a pill but as a nutrient in my food?
Over my typical Monday-morning breakfast (a bar of chocolate, washed down with a cup of espresso), I began to look for advice about what I should be eating to feel better. One website, from the Cleveland Clinic, advised five servings of grains, two servings of vegetables and limited fat to aid with wound-healing. Another article urged quite the opposite: a high-fat, high-protein, low-carbohydrate diet. Yet others suggested zinc, or vitamin D, or enough supplements to clean out the health-foods section of my local grocery.
The smatterings of advice gathered from the internet prompted a thought experiment. What if you went to your doctor with a specific condition, and she prescribed a medicine? But when you asked her why you were taking this pill, she said, "Oh, because your ancestors took it." Or "because it tastes good," or, worse, "because it was what the pharmaceutical industry could make most profitably and effectively."
Most of us, I imagine, would find ourselves irate over such answers. Yet we blithely accept these standards for human diet: We are stuck with our diets because our ancestors ate this way, because food tastes good or because agribusiness has persuaded us about dietary compositions. Unlike most medicines, whose effects we sift, measure and scrutinize, often using the most rigorous clinical trials, human diets — the other set of molecules we put into our bodies — have gone relatively unexamined. We are living in a molecular age of targeted therapies, in which strategies like immune modulation, genome sequencing and gene editing are used to probe and alter human biology. And yet, while aspects of human diet have undoubtedly changed, we may be eating what we eat for no good reason at all.
Several months before my surgical procedure, a cancer patient asked me whether she should change her diet. She had lost her appetite. One nutritionist had advised her to start consuming highly caloric, sugar-loaded drinks to maintain her body weight. But, she worried, what if the sugar ended up "feeding" her cancer? Her anxiety was built on nearly eight decades of science: In the 1920s, Otto Warburg, a German physiologist, demonstrated that tumor cells, unlike most normal cells, metabolize glucose using alternative pathways to sustain their rapid growth, provoking the idea that sugar might promote tumor growth.
You might therefore expect the medical literature on "sugar feeding cancer" to be rich with deep randomized or prospective studies. Instead, when I searched, I could find only a handful of such trials. In 2012, a team at the Dana-Farber Cancer Institute in Boston divided patients with Stage 3 colon cancer into different groups based on their dietary consumption, and determined their survival and rate of relapse. The study generated provocative data — but far from an open-and-shut case. Patients whose diets consisted of foods with a high glycemic load (a measure of how much blood glucose rises after eating a typical portion of a food) generally had shorter survival than patients with lower glycemic load. But a higher glycemic index (a measure of how much 50 grams of carbohydrate from a food, which may require eating a huge portion, raises blood glucose) or total fructose intake had no significant association with overall survival or relapse.
While the effect of sugar on cancer was being explored in scattered studies, the so-called ketogenic diet, which consists of high fat, moderate protein and low carbohydrate, was also being promoted. It isn't sugars that are feeding the tumor, the logic runs. It's insulin — the hormone that is released when glucose enters the blood. By reducing carbohydrates and thus keeping a strong curb on insulin, the keto diet would decrease the insulin exposure of tumor cells, and so restrict tumor growth. Yet the search for "ketogenic diet, randomized study and cancer" in the National Library of Medicine database returned a mere 11 articles. Not one of them reported an effect on a patient's survival, or relapse.
But what if diet, rather than acting alone, collaborates with a drug to produce an effect on a tumor? In the winter of 2016, I had dinner with Lewis Cantley, director of the Meyer Cancer Center at Weill Cornell Medicine. Decades ago, Cantley discovered an enzyme named PI3 kinase, which regulates the growth and survival of cells in the presence of nutrients. By inhibiting this enzyme using novel drugs, researchers had hoped to target the signals used by tumor cells to grow, thus "starving" the cancer. But the drugs designed thus far were only marginally effective. Why, we wondered over salmon teriyaki in a nondescript Upper East Side joint, might blocking such a central hub of growth activity have had only a modest effect on tumor growth?
The trials gave us a crucial, obvious clue that we had missed: Many patients had become diabetic, a phenomenon seen as a side effect of the drug that had been ignored. Perhaps the drug wasn't just providing a "starvationlike" signal only to the tumor cells, we speculated. As most drugs do, the molecule circulated through the entire body of the patient and also acted on the liver, which sensed the same starvationlike signal and, as a reflexive response, sent glucose soaring into the blood. The glucose, in turn, most likely incited insulin release in the pancreas. And some patients treated with the medicine returned to the clinic with sky-high levels of glucose and insulin — in essence, in the throes of drug-induced diabetes.
Cantley wondered whether the additional insulin was reactivating the signals within the tumor cells that had been shut off by the PI3 kinase inhibitor, and so allowing the cells to survive — in effect, undoing all the good being done by the drug. On a paper napkin borrowed from the waiter, he drew out a scheme to outwit this vicious cycle. What if we cut off all extra insulin released, by putting patients on a low-carb, ketogenic diet while on the drug? It would be a novel kind of trial — one in which diet itself would become a drug, or a co-drug, with the PI3 kinase inhibitors.
Between 2016 and 2018, postdoctoral researchers in Cantley's laboratory and mine established that this strategy worked on several mouse cancers, and on human cancers implanted into mice. By 2019, working with clinicians at Columbia, Cornell and Memorial Sloan Kettering, we hope to begin a study in humans with lymphomas, endometrial cancer and breast cancer, to use ketogenic diets in concert with the PI3 kinase inhibitors. (In the meantime, a host of other studies have also demonstrated that other diets could potently modulate the effects of targeted therapies on cancers in mouse models.)
But the experiments on mice also warned us of an important pitfall of such an approach. While the "drug plus diet" model worked on experimental mouse and human cancers, the ketogenic diet had a limited effect by itself. For some cancers in the mouse models, the keto diet alone kept the tumor growth at bay. But for others, like some leukemias implanted into mice, the diet alone accelerated the cancer, while the drug-plus-diet approach slowed it down.
We published this data in the scientific journal Nature early this year. I sent out a tweet with the results, emphasizing that the human trial was about to be started, and that the keto diet alone might have a negative effect on some tumors — in essence, a "folks, don't try this at home" message. The response over social media was unexpected — brisk, vicious, angry, suspicious and, at times, funny. " 'Keto' is pure hype," one responder wrote. Another countered: "Who is supporting you? Big Kale?" One writer proposed returning to an ancient diet — "deer, rabbit, river fish" and "wild birds." Yet others blamed me for undermining the effectiveness of the ketogenic diet in cancer.
The vituperative, emotional response to this study illustrates the doubt and anxiety that any conversation about human diets incites in the public realm. A careful scientific examination of diet as medicine is now long overdue in oncology, and in most fields of medicine. There's an interaction of our diets with our gut microbes that remains to be examined, and the impact of diet on longevity, on neurological diseases or even on mental states. Perhaps we need to rebuild the human diet from scratch, much as we built our medical pharmacopoeia: Rather than relying on received knowledge, or on presumed ideas, we might examine our diet molecule by molecule, and trial by trial, probing the aspects of food that incite or treat particular diseases, for particular humans, with particular genetic attributes. In the age of molecular therapeutics, perhaps we might need to rethink diet, too, as a form of molecular therapy.
Siddhartha Mukherjeeis the author of "The Emperor of All Maladies: A Biography of Cancer" and, more recently, "The Gene: An Intimate History.""
Wow! Thanks for sharing this article. I read the NYT every day and somehow missed it. Love Siddhartha Mukherjeeis.
I agree that diet must profoundly influence our health even more so when we have cancer. But, as he says, we don't have much information about what would help and what would hurt. My biggest question about the vilification of white sugar is that your body turns all carbohydrates into glucose, not just that piece of candy. There are carbohydrates in most foods we eat. Unless you go on a strict ketonic diet, your body will be turning everything it can into glucose. Then there's the question of how high ketone levels can also be harmful. I love his stance that we should not go by the "just keep eating what we've always been eating" attitude. We need to find out what is best and what is best for each person must be highly varied. It's similar to the way, the more we learn about cancer, the more realize how complex and varied cancer cells are and the specifics of the host of those cancer cells makes solving the puzzle even more difficult. They used to talk about finding a cure for cancer. It seems unlikely that there could be a single cure for everyone's cancer. He talked about this in "The Emperor of Maladies".
Just got my latest scan results back today. I am stable versus three months ago but was disappointed that the dramatic tumor reduction I saw after the first scan did not seem to continue. It could very well be that my body is producing too much insulin in response to the high blood sugar levels triggered by the Alpelisib. Variation in my consumption of carbs has not seemed to change these levels but I have not tried getting into ketosis. I'm thinking of trying it out until my next scan to see if it makes a difference. Will have to be careful to stay hydrated to protect my kidneys.
Loving the high level of participation from Canada on this thread!
Susan I agree, also wondering why he didn't touch on that here. It seems to be quite a hard diet to sustain although if I remember correctly Zarovka managed to do it and she posted quite a bit on the process. The word "diet" usually has me running for the hills. Hope the trials go ahead in the new year to get a definitive answer. Congratulations with your continued success!
Latest side effect. My hair has been thinning out. Don't know if it's the Letrozole or the Alpelisib. Not quite to the point of shaving it all off but on the borderline.
Other than this latest SE, probably the letrozole, I'm happy that you're tolerating/thriving? on the trial Susan. I had quite a bit of hair thinning on letrozole. Hair is starting to thicken up now that I've been off it for a couple of months.
Hi Susan, Are you hanging in there? You must have been one of the last people allowed on the trial, because the form says it is active but no longer recruiting.
There are reports that inhibiting PI3K can not only make the cancer regain sensitivity to estrogen, but also to Ibrance, so maybe if your great results start to plateau out, you might ask about adding some Ibrance back into the mix?
Dee, Thanks for telling me about your hair loss on Letrozole. My MO said I could try Rogaine. Ordered some on Amazon. Don't mind being bald but right now I have too much hair to be bald but so little that I have trouble styling it to cover up bald patches.
Cure-ious, Wow. I didn't know that the trial was no longer recruiting. I figured that the barriers to entry were so high they would have trouble filling all of the spots. Hope it's not because they are seeing too many horrible reactions like those experienced by the other women on this board. And thanks for the information about regaining sensitivity to estrogen and Ibrance. Have been on a keto diet for just over a week. Got into a state of ketosis in less than two days but the last two days I seem to have slipped out. Guess I'm not tracking my carb intake closely enough. Even if I'm not in ketosis all of the time, at least my carb intake is far lower than it was before. My bloodwork last Tuesday showed a fasting glucose level of 78. Have been doing pretty well. Terrible allergies which is strange since I'm on a double dosage of antihistamines.
I think the confusion is that the Solar trial is no longer recruiting, but the Bylieve trial just started. That is the trial I’m on and maybe Susan too
"The ongoing phase 3 SOLAR-1 trial (NCT02437318) is evaluating ALP + FUL combination in HR+, HER2– aBC. The present BYLieve study aims to assess the efficacy and safety of ALP + FUL/LET in PIK3CA-mutant, HR+, HER2– aBC progressing on/after prior CDK4/6i combination therapy."
So, it sounds like SOLAR-1 was successful (although they were criticized for taking so many patients without PI3K mutations, who they knew they were not likely to respond!), and now the BYLIEVE trial is seeing if they get comparable or different results for patient who previously took Ibrance. So would FDA approve Alpelisib based just on SOLAR-1, or would they need to get the data from BYLIEVE now that most of their potential users would have already had Ibrance? And if its the latter, why didn't they just make a subgroup to SOLAR-1 consisting of previous Ibrance users? Maybe they expect comparable results but have a better idea of the dose range and will only test PI3K mutant patients and in that way get better PFS numbers?
The trials have different exclusion/inclusion criterion. I suppose as they saw the preliminary results of SOLAR-1 they figured out who was most likely to be successful and winnowed that group down for the BYLieve study. For example, to be on the BYLieve trial you can't have been on more than two previous treatments. SOLAR-1 says no one who has been on chemo which would have excluded people like me who took Xeloda, a common first line chemo. I only want to be on Phase II trials because then I'm sure to get the treatment. No placebo group. Preferably a Phase II for a drug that has already passed a Phase III trial. I was on an Ibrance trial after it was FDA approved. The trials compared dosages. When I'm on a trial, besides having them pay for the drug, I receive the services of a trial coordinator who books all of my appointments, gets me my meds and does all the paperwork.
Just wanted to check in to see how everyone is doing. And maybe celebrate a little bit because I just passed the one year mark on my clinical trial, which is alsotesting a pi3kca inhibitor just not alpesib.
Congratulations! That gives me hope! So far, I really like the Alpelisib + Letrozole. I'm happy with any oral treatment that works without horrible side effects. Being on a keto diet kind of sucks but it did seem to bring my Hemoglobin a1C down so I'm going to stick with it. Have my scans next week. Hopefully, it is still working.
NewGardener, Are you taking ipatasertib? Do you have a sugar-restricted diet, and what side effects do you have, a year in?!
Susan, How funny, I was just wondering how you are doing and if you are still in the trial?!! Especially since you almost didn't get in- twice!!! Everyone is waiting to see if it gets FDA approved, and if so, how they will be testing us for PI3K mutations.. Good luck with the scans!!
I was thinking about Susan this week too, wondering how you're doing? I'm still on the trial just not taking alpelisib but getting fulvestrant. I'm glad you are tolerating the drug ok & wish you all the best for good scans. My last scans showed a tiny bit of progression but that was in December, very shortly after changing treatments. Next scans are in 2 weeks, yikes.
Wishing the best for your scans too, Dee!
Hi SusaninSF. You have probably already mentioned this, but do have the Pi3K mutation? and if so, was it found via tumor genetic testing or liquid bx? Just gathering info..