How are people with liver mets doing?
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Right now only at Vanderbilt, but will be opening up at UCSF and Memorial Sloan Kettering
Can have prior CDK4,6 inhibition but not more than two standard chemotherapy treatments, no herbal or other anti-cancer regimens are allowed during the trial
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Z, below is the FGF/FGFR trial my MO told me about yesterday. I also have a mess of FGF/FGFR mutations. I initially thought he was directing me back to a study we looked into for FGFR1 but after reviewing the trial today, I see this is different. It is being given as a single agent and now with several other drugs as well. There must be more locations than is showing in the attached because the location near me my MO mentioned is not yet listed.
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KC1010, thanks for sharing your experience with Guardant. I am also on chemo so that could skew my results as well. When I asked my MO whether it is as effective as a Foundation One or Caris panel, he said "Well, they convinced the FDA to approve it as producing similar results to Foundation One and Caris". I take that to mean the jury is still out with him on how good the test is but it must have some efficacy if it could clear the approval process. Good luck with Xeloda. Such a great drug. My favorite line of treatment to date (including hormone therapies).
Cure-ious - You mentioned FGFR drugs perhaps being a better treatment than mTOR/PI3K drugs. Does that mean research is finding a link between FGFR and the PI3K pathway? I noticed something in my MOs notes from yesterday's appointment where he mentioned my mutations of those two in the same context and I couldn't figure out why.
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Z and JFL- For one thing, I think mutation in mTOR/PI3K and amplification of FGFR are different mechanisms by which resistance to CDK4,6 inhibitor might develop, so inhibiting either pathway might be effective to block growth and and may also make the cancer responsive to Ibrance again, which is why some trials are giving these FGFR inhibitor drugs together with Ibrance and Faslodex.
I was just reading a bit about the FGFR data- AMPLIFICATION of the FGFR gene (where the cancer cells have extra copies of the gene) is more common than having MUTATION of the FGFR protein. The data indicate that amplification of the FGFR gene more clearly indicates that it is actually driving the growth of those cancer cells, whereas FGFR mutations are less common, and depending on what exact mutation it is, may or may not affect the growth of the cancer So read your genomic analysis carefully to see if you have amplification or mutation of FGFR-
I believe that to qualify for the trial I mentioned above you would have to have FGFR-AMPLIFIED metastatic breast cancer (and should also still be classified ER-positive, HER2-negative). So the idea is that FGFR ampification may help the cancer to resist the Ibrance-Femara, and the trial is checking if a good next treatment would be Faslodex (to overcome the Femara resistance) in combination with the FGFR inhibitor (to block growth of the resistant cells and restore sensitivity to Ibrance) and Ibrance. In the clip, they mention this FGFR inhibitor is potent and that the pre-clinical data looked good at the San Antonio 2017 meeting.
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JFL- I think you might also be eligible for the afore-mentioned trial, in addition to the one your ONC recommended, because you have not had more than two chemotherapy regimens in the metastatic setting. However, your MO may think that hormonals will no longer be effective for you? and the trial he brought up does include an FGFR-inhibitor with Keytruda (checkpoint inhibitor) or with some other combinations. The trial does monitor serum FGFR levels and will be looking to see if the degree of amplification correlates with how well the drug works, so it is possible they might know rather quickly whether the drug is at least working to reduce FGFR over-expression (and then scans will say whether reducing FGFR correlates with stable disease outcome)...
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Cure-ious, thanks for the explanation and additional info! I have an FGFR1 amplification and FGF3 amplification (no FGFR/FGF mutations - I was using that word too loosely/incorrectly). My F1 report indicated I have 1 mutation (PIK3CA N345K) and 6 amplifications in total. My MO is not opposed to hormone therapy but my liver needed chemo to tame things down and I am likely resistant to any hormone therapy alone at this point and would probably need it combined with at least 2 targeted therapies attacking different pathways to have a chance of anything working. (My prior treatment, Afinitor/Aromasin, was not effective at stopping my liver tumor growth but it did slow it substantially so it had *some* impact.) I will look into the links you posted. I have already taken Faslodex which might be an issue.
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JFL- It says no limit on former endocrine therapy, so previous Faslodex not an issue. I will read up more on the FGFR inhibitors in these trials..
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Cure-ious I mis-spoke. I have a hot mess of FGFR AMPLIFICATIONS ...
Gene ........9/22/17.....11/19/17 Caris
CCND1 ~10X Ampl ~4X amplification
FGFR1 ~10X Ampl ~4X amplification
FGF19 ~10X Ampl Not reported
FGF4 ~10X Ampl ~4X amplification
I had to call Caris for these amplifications because they don't report amplification unless it exceeds 6X or 7X.
JFL - read up on side effects as well. Some of the FGFR targeted therapies have not advanced in clinical trials due to severe side effects. This is a decent review of the whole class of FGFR drugs that you can access for free. I got deep into this topic when I got my Caris and F1 reports back.
FGFR a promising druggable target in cancer: Molecular biology and new drugs
This is the blog of a lady who has been through 3 FGFR targeted drug trials. Or rather she is in the middle of her third. She has cancer of the bile duct and not a lot of options. She discusses the side effects of the drugs, including INCB054828, the drug in the above referenced trial.
http://pattysjourneyoffaith.blogspot.com/
>Z<
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Here is the conclusion from an abstract at San Antonio from the Vanderbilt group about FGFR amplification:
Conclusions: These data suggest aberrant FGFR signaling is a mechanism of resistance to anti-ER therapies ± CDK4/6 inhibitors. We posit overexpression of cyclin D1 induced by both FGFR signaling and ER transcription plays a role in drug resistance. Based on these findings we propose ER+/FGFR1 amplified breast cancers are endocrine resistant and should be candidates for treatment with combinations of ER and FGFR antagonists. Accordingly, we have initiated a phase Ib trial of fulvestrant, palbociclib and erdafitinib in patients with antiestrogen resistant ER+/HER2-negative breast cancer with FGFR1-4 amplification.
Basically they are saying that one common way to get resistance of cancer to Ibrance-Femara is to increase FGFR, which turns on Cyclin D (an activator of CDK4,6) and therefore the cells have elevated CDK4,6 activity and can grow in the presence of Ibrance. So they are suggesting that if you get rid of the increased FGFR activity in these cells, then the Cyclin D levels will go back down, and the CDK4,6 activity will go down to normal levels, at which point it can now be effectively inhibited by Ibrance as it was before the FGFR got amplified.
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Z: did they have to rerun your tests that were less than 6x or 7x or did you just have to call and ask them to report out all amps with any amplifications?
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They have the amplifications of the genes that did not meet their reporting threshold and you can call them for this information. I called them a few times with questions and then at some point they realized they were talking to the patient not the doctor's office and they refused to talk to me further. After that I fed a few questions through my doctor.
The Caris test is, overall, among the most robust tests but if you don't know how they operate, you can have issues. Caris lists a bizzilion biomarkers on their website that they are capable of testing for and in fact they test for almost all of them routinely. Stuff with no known relevance to treatment protocols is included. However, they still make an internal decision regarding whether to include certain tests, supposedly based on relevance to the type of cancer. In my case, however, they excluded tests that would be relevant to the treatment of MBC. Their decision process looks random to me. Left me furious for a week.
But I now know that I if I am interested in a specific marker or gene, I have to specify it in the order or it may not be tested. They can't retest without more sample, which is typically not available. To be sure to get what you are interested in, you have to specify up front what you want.
Another thing with all these genetic tests is that they need a lot of tissue and specifically a lot of useable tissue. The problem with biopsying a tumor is that 80% of a typical tumor is dead. The Caris test was the second test I did. By the time I did Caris, Ihad learned a bit and I told the IR to get TWICE the number of cores Caris needed. I was hoping to have a little bit left for additional testing by my local pathologist. In the end Caris needed every core. You get unusable cores and cores with limited viable cells and the total number of useful cores is pretty low. The IR was clueless on this point and challenged me. I had to tell her that I was doing additional private testing beyond Caris to get her to pull the cores. In the end we barely got what was needed for Caris
>Z<
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When I start looking at a class of drugs I go to selleckchem.com and look up the drug. For each drug they show a chart that includes all the drugs in that class of drug and some measure of it's activity against the desired targets. The activity is measured typically in vitro but they have references to their data sources that you can use to track down what they were really measuring.
This is their chart for FGFR inhibitors. The graphic is bad but you just go to their site and search for any one FGFR inhibitor and the report will include this chart.
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Z you are such a giving person. Taking the time to respond to everyone when you are dealing with so much. I will be thinking of you on the long flight home, All that treatment will work see it and believe it. Add mindfulness and visualization to the mix, what do you have to loose
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Hello. Zarovka I wish you the best effect of your treatment in Japan as well the best luck to all of you ladies. I felt really sick after I finished fever week with interleukin and last dose of nivolumab. My ALT have risen 6 times above normal values. I have it always from medicaments. After week I am back to my normal and right now I am skiing in Italy. I hope the therapy killed all the bad left cells in my body. I will have mri within two weeks.
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Maaaki - I am so interested in your story, particularly because it ends with a ski trip to Italy. Please keep posting any details. Because of your post I asked my doctor in Japan about combining interleukin with the immunotherapy I am doing. He does use interleukin and it does a great job driving the immune response. He usually only does interleukin with Japanese patients because of the fever; however, he is willing to consider it for me next time since he has gotten to know me. There is already one person who has gotten treatment changing information from your post. Please keep it coming.
bstein - thank you for thinking of me. It means a lot.
I am back in the US. This time the treatment was tough. I am still exhausted even though my last treatment was Friday. Since Saturday, my abdomen has been in a lot of pain ... a lot of cramping, burping, gas. My solar plexus feels like I did too many situps, although I am not doing ab work. For the moment I am trying to get rest see and see if it resolves with time. It's a little better, but not obviously significantly better at this time. Terribly gassy and burpy so at least part of it is a gastric issue.
>Z<
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I'm glad you're back in your own home with your kitties, I hope.
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Z:thank you so much for the information about Caris and the other website. So appreciate you sharing
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Have not posted here in a while, but have been following. Falsodex has not worked for me-progression in liver. Meet with MO in the morning to discuss new treatment modality. Bummed. MJH
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Hugs MJH. Interested in your choices and thinking process.
>Z<
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babs, Great news about Y90. May it last forever!
To be honest I feel so lost in all of the discussions on mutation, expressions, what test tells what. I wish I was more of an analytical scientific mind to grasp it all as I feel I am not asking critical questions of my Onc. He seems to be on top of things but at a minimum which makes me feel like a throwaway. I feel like I need to start at square one and get more educated but when I feel like CRAP it's really hard.
Anyway, started Gemzar a week ago, woke up this morning very short of breath and absolutely exhausted. So they had to hold treatment already and send me for a scan to look for blood clot or pleural effusion. Wish I could just catch a break soon. I am very worn out......
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Welcome Home Z - Warrior princess! Your knowledge and encouragement inspire us all. When will you know if this procedure/process worked? Glad you are still on fulvestrant. JFL - glad you could stay on A-train. Robin -rooting for your TMs to really drop on A-train! Please PM me. Shetland Pony I miss you. My journey into 3 weeks of skull rads hell ended today. This stuff is awful. I lost some of my well preserved cold cap hair, and have a sunburned scalp and forehead to even things out. oy Plus from my bathroom fall a healing black eye and a bruised split lip. Needless to say with all the mouth blisters I lost another 7 pounds. I now have to get IV fluids every other day to keep BP up. Catching up on posts today. Artist - rooting for you on Gemzar - will you lose your hair? Kation how are you and Gemzar doing?
(()) Claire back from the hospital
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Artist. Here’s to your catching that beak that you so deserve!!!
Bab
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Artist, How disappointed you must be after waiting so long to restart treatment. I hope that the tests for blood clots and pleural effusion are negative and also that the shortness of breath is resolved. I understand why you are so worn out. You have been through so much, even facing a struggle getting COBRA in place. It's time for things to turn around for you and get better. I hope that happens very soon and that treatments resume quickly and beat down those cancer cells. You should never feel like a throwaway, and I am angry that you have been made to feel that way. Your MO and everyone else involved in your treatment should focus on you, your health, your feelings, your well-being, and your needs and wishes whenever they see you, talk to you, review your records, and research the treatment options. Don't worry about mutations, expressions and testing right now. You can research all that when you feel stronger. Sending you warm (((hugs))).
Hugs and prayers from, Lynne
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Artist and lalady (and all)
I just got home from Gemzar #2. My neutrophils where a little low, but since monocytes are fighting the good fight, they went ahead and gave me the treatment. It is certainly tiring. Have to watch my fever.
Artist, I hope your tests today are helpful. I hate that you cannot get a break!
Lalady, I did not know about your fall. Gee! Hope the worst is behind you. It does take time to recover from brain rads. Let yourself rest and eat whatever you can.
Been a tough week on bco. Here’s to Spring and better news!
Hugs to all.
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Hi Ladies,
Had my week three abraxane today. My WBC did not tank this time! My onc did not do tumor markers today, so I don't know when I will find out if this is working or not. I am going to try to go to back to work on the 16th. I hope I can do it.
It has been a tough week on the thread. I marvel at how upbeat and positive you all are.
Z-hope you are feeling better!
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Artist. I thought I was really understanding a lot about F1 report. Asked a few questions today at MO appointment, now i feel like you. OMG. I'm so deflated.
I'll write more tomorrow, I'm completely brain dead tonight. 💞
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Met with my MO today. She wants me to stay on Doxil at least until after the Y90 on 4/6. Since its working on the liver mets she wants to bang the dickens out of the liver before we make any changes. Sounded reasonable to me so I agreed and had my infusion tonight. Plus, she said that the radiologist felt that what is going on in my lungs is more inflammatory in nature. Hope so!
Babs
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Lalady - Congrats on completing radiation!!! Huge empathy regarding skin and hair. I am a wreck with any symptoms or side effects. Dealing with gastric issues and fatigue after returning. There is something wrong with my gall bladder. Bile in urine ... urine is yellow and foaming. Pain around gall bladder. Possibly tumors pressing on the gall bladder, interfering with the normal processing of bile. Bile in serum not excessively high but I have Graves disease (normally high bilirubin) which confuses the signal.
Improving daily which gives me some optimism. Experiencing huge ups and downs as I deal with the uncertainty of whether my current strategy is working and the prospect of systemic chemo if it doesn't.
Weird dry skin near one corner of my mouth developed today ... the skin sort of dies and peals off. Not quite bleeding but leaves open raw skin as the dry skin falls off. Curious if anyone knows what to do. Any symptoms that other people can see make me very upset.
So ... huge empathy to Lalady ... you are so strong to get through that radiation. It is the corner stone of your treatment strategy to get those skull mets controlled, so well done. Hard part over. I hope a lot of rest is scheduled for the coming days.
It is a tough tough time on BCO. Hugs and support all around.
Babs - Thanks for the update. Very interested in how doxil goes for you. My father has prostate cancer. He had a more or less miraculous response to doxil. He is entirely off treatment now. I am hoping I got those Miraculous Response to Doxil genes.
JFL - I know you are headed for local liver treatment. Are you still evaluating those FGFR trials for the future? One of my advisors is really pushing me to get one of these FGFR inhibitors in the next few months. I am getting back into my research from the fall and trying to figure out what is going on with this line of research.
>Z<
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Z, I contacted the trial and have received a few short responses from the coordinator. The coordinator told me the trial was only recruiting FGFR "mutations" at this time but when I mentioned I have FGFR1 and FGF3 amplifications, she asked me to send my F1 report. Hoping that is a good sign. My MO said that this trial didn't note an express requirement the report be from the last 6 months, like the prior FGFR1 trial I looked into last summer. The botched biopsy closed the door on that trial. I wouldn't mind getting another biopsy if it is needed because I still want a Caris report.
LA, congrats on graduating from skull rads! Your fall sounds just awful. Ouch. I am glad you are okay.
Babs, how long did your MO & IR require you remain off chemo before your Y90? Amazing they let you start back up again after less than a week. Was that their idea? I ask because I don't like the idea of having any break from treatment for my Y90.
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JFL and Z. I was never off treatment. I started Doxil in December it’s once monthly. I can’t afford to be off treatment with this beast inside me. My last scans while on Doxil were mixed. Really good response in liver. But slight increases in bones and lungs which they now think is more inflammatory in nature. But my mo really wants to attack the liver with everything we can. Fingers crossed
Babs
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