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karen1
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Topic: New to Mets - Treatment advise Posted: Aug 01 2013 at 11:23pm |
Hi all I was diagnosed with a very aggressive stage 3 TNBC when pregnant with my 3rd child in September. I now have an 8 month old, 6, and 8 year old and am very scared for our future. I have had AC/Taxol, mx, radiation, and cisplatin/parp trial (didn't get the parp). My cancer was very unresponsive to chemos but I was NED for a few months. I have been in treatment of some type since this all started! Last week (and one month after finishing the cisplatin trial) I was diagnosed with skin and lung mets. I am now scrambling to make the best next move. I have had 2nd opinion at MD Anderson and was told I would live maybe a year since my cancer is so aggressive and didnt respond well to prior chemos. She suggested finding a stage 1 trial or start with zeloda/ixempra (which sounds pretty hardcore for my first hit at these mets and bad side effects Ive heard). I am losing hope, dont know the best move and with the children this has been very stressful. I have a great oncologist at Northwestern in Chicago but feel I have been left to make my own decision. Should I go with a standard treatment as my first try at these mets and if so which one. Should I find a phase 1 or 2 clinical trial with one of the new inhibitors plus a chemo or one of these new immune booster drugs (they all seem to be unnamed)? I feel like I need to move quickly to prevent spread. Any suggestions are welcome.
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Tonya98
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Posted: Aug 02 2013 at 11:56am |
Hi Karen, I am truly sorry this is happening but I wanted to offer you some hope. I was aggressive stage 3, had remission for about 4 months, then spread. That was six years ago. It is a matter of finding a treatment that works. Even though it is scary, we are often the ones that make the decisions based on the doctor's recommendations. A second opinion can be helpful also. Phase 1 trials are to determine if the drug works. Phase 2 trials are where they know the drug works but are trying to figure out the dosages. Proven drugs like Xeloda/Ixempra have been successful on some patients. It may also take time to get into a trial whereas you could start other drugs right away. I'm sure others will respond with more thoughts. Hugs, Tonya
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2/1/07 -IDC 2.5cm node positive her2+ ACT&herceptin.
1/8/08 recurrence to skin -triple negative. 07/23/10 -chest wall. Parp trial 9/10 - present. Iniparib ending November 2015 Stable 9/19/2016
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Kitkat
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Posted: Aug 02 2013 at 8:51pm |
Karen...never give up Hope!!! I was on Xeloda, had good results for 2 months....3 months later, tumors had gone from 4-7 and tripled in size. I am on Doxil now, it normally is given to gynocalogical cancers...but as you know TN is more like those cancers then bc. If you read other post. It's just a matter of finding what works for our on cancer. MDAnderson has a handful of trials coming up in 2014. Keep that in mind, but only do phase 2 trials or higher, no phase 1. My dr. Told me he has several tricks in his bag of tricks for me....never give up. Those babies are counting on you!!! Hugs girl friend :)
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Dx 6-10 stage 1, grade 3, 1.2 cm tumor w microvascular invasion, CTx4. 25 rads w 7 boost. 1-13 stage 4 w 4-1 cm tumors to lungs. Xeloda 1500x 2 a day, ct scan 3-29, 50% shrinkage! Hopin and praying
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btstark2003
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Posted: Aug 05 2013 at 6:28pm |
Kitkat,
Don't be so sure about dismissing Ph1 trials, girlfriend! Somebody has to be the first to try a new combination in order for a treatment to ever be made available for the rest of us, and depending on the stage of your disease and how much is known about the study drug, it may be worth the risk.
I know that Ph1 sounds scary, but sometimes a Ph1 trial is a new combination of a well-known drug with a study drug that has already been given to quite a few people, which really reduces the risk. That was the case for me with the PI3Ki drug BAY80-6946 given in combination with paclitaxel (Taxol). And it dissolved all my lung mets in 6 months and now I am NED and feeling great! 3 months and counting! So I think that going on a Ph1 clinical study saved my life.
Karen1,
YOu may want to ask your docs about the Ph1 trial of BAY80-6946 in combo with paclitaxel. According to clinicaltrials.gov this trial is stillrecruiting in both St. Louis (where I had treatment at the Siteman Cancer Center) and in Houston (I assume MD Anderson) - It worked for me (I had 5 lung mets with the biggest at 2 cm) and got me to NED in 6 months and I tolerated really well for 5 months, working full time while the mets steadily shrank, and then I developed an immune respone during the last month but it wasn't that bad. And I know that at least one other Stage IV TNBC patient also had a CR (complete response).
This was my 4th chemo regimen and while it was time consuming (2 infusions per week on successive days, every week), I did not have much fatigue at all like I did with all the other regimens.
If you would like to know more, I will send you a PM with my phone number so that you can call me. I agree that you need to move fast but it can be done! From the time my lung mets were diagnosed last Halloween until the day I started the Ph1 study was only 12 days.
I know how scary this is. I certainly didn't have a baby when I had mets, but when I was first diagnosed my girls were 6 and 9, and now they are 11 and 14. I plan to have many more active years with them.
Beth
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2008 Stg1 TNBC, LX, FEC+T, rads 2010 2.5cm tumor BRCA-, BMX,CMF 2011 LN mets, Gem/Carbo, surgery, rads 2012 lung mets, PI3Ki/taxo 2013 anti-PD-1 2014/15 Xeloda, IMMU-132, eribulin Aug 2015 Keytruda
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karen1
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Posted: Aug 05 2013 at 7:27pm |
Thanks for the words of encouragement! KitKat were you tested for the KI3 mutation before joining the trial? I spoke with Dana Farber who is doing many Kinase inhibitor Ph 1 studies and they said I would have to be tested for the mutation of these inhibitor drugs would be a waste on me and that would take 2 weeks. Doctors want me to start something now and hope I am a match for a clinical trial after this 1st standard treatment. One doc says start with Xeloda +avastin and the other says Iribulin/Halevan. THis is all just a guessing game and very hard when 2 TNBC experts say 2 different things!
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karen1
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Posted: Aug 05 2013 at 7:29pm |
sorry I meant to direct that trial question to Beth :) Also Beth did you have taxol prior to starting the trial?
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Kitkat
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Posted: Aug 05 2013 at 8:12pm |
I was going on what my dr said. I will ask him about that one. I have not had a K13 test. I will ask about that one, thank you Beth :))
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Dx 6-10 stage 1, grade 3, 1.2 cm tumor w microvascular invasion, CTx4. 25 rads w 7 boost. 1-13 stage 4 w 4-1 cm tumors to lungs. Xeloda 1500x 2 a day, ct scan 3-29, 50% shrinkage! Hopin and praying
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btstark2003
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Posted: Aug 05 2013 at 11:26pm |
Karen1,
My tumor was sequenced for a panel of genes after my 3rd occurrence while I was on a Gem/Carbo regimen (I had a partial response to that, followed by surgery). I did not have a mutation in the PI3K gene.
When I had the 4th occurrence (lung mets), my doc said that I could still have a mutation in one of the other genes in the PI3K pathway that were not tested, and he also thought that research is showing that the PI3K pathway may be a critical survival pathway for many TNBCs, so if you inhibit PI3k while also giving a chemotoxin such as paclitaxel the TNBC cells may not be able to survive. So he thought that study was my best shot. Having the PI3k tested was was not an entrance criteria for this clinical study. I had never had taxol prior to this study, though I did have 3 cycles of taxotere as part of an FEC+T regimen as adjuvant therapy after my first occurrence.
One advantage of a Ph1 study is there is no randomization to different arms - you know that you will get the study drug :-)
That said, it totally makes sense to go on one of the non-study regimens that either of the TNBC experts recommended so that you can start something quickly and see if it works. If they can't tell you why one of the regimens might be better than the other, perhaps you could make the decision based on which one tends to produce milder side effects? For me, it was really important once I got to Stage IV to factor in my quality of life in the treatment decision. Beth
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2008 Stg1 TNBC, LX, FEC+T, rads 2010 2.5cm tumor BRCA-, BMX,CMF 2011 LN mets, Gem/Carbo, surgery, rads 2012 lung mets, PI3Ki/taxo 2013 anti-PD-1 2014/15 Xeloda, IMMU-132, eribulin Aug 2015 Keytruda
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amylynn
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Posted: Aug 05 2013 at 11:49pm |
Hi Karen, Just wanted say Hi and it sounds that you have gotten some good advice. Please look at all clinical trials. They could be promising, even if only a phase 1 trial. You have to weigh the good and bad with each option and see if its doable for you. Anyway, prayers to you and your family. I hope you are able to make a decision soon and that its easy to deal with and has minimal side effects. Take Care.
Amy
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36 at dx IDC 2/09, 8cmx3cm grade 3,BRCA1, Cl Trial-4- Taxotere,4-AC,6-Avastin,4 cycl Xeloda
9/09-rght mast.w/tissue exp
PCR
Avastin x10,28 rads,done 7/10
left mast/w bi-lat DIEP & OOPH
Mets 6/2012
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Grateful for today
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Posted: Aug 06 2013 at 1:19am |
Karen,
Just wanted to send some caring and good thoughts your way. I have not had the experience you are having now about deciding on treatment for recurrent disease. I cannot begin to imagine what you are going thru. Wanted to share the quote that I have posted before on other forums: Statement by Jerome Groopman, MD in his book: "Anatomy of Hope". " Each disease is uncertain in its outcome and within that uncertainly we find real hope, because a tumor has not always read the textbook, and a treatment can have an unexpectedly dramatic impact. This is the great paradox of true hope. Because nothing is absolutely determined, there is not only reason to fear but also reason to hope."
Sometimes thoughts for consideration (never advice) will come into my mind when I read a thread. When I am not sure whether to post them or not..........I say, please disregard the following if not helpful.
Thus, please disregard the following if not helpful. Or if you have already made a decision, just disregard the following. Seems a big plus you are able to say: "I have great oncologist at Northwestern in Chicago" When I read your " but feel I have been left to make my own decision", had some thoughts for consideration. Wondering if you can sit down with your oncologist and discuss something like: 2 TNBC experts suggest 2 different plans and also mention Ph1 trial of BAY80-6946 in combo with paclitaxel (that Beth mentioned above). Would your onc consider calling a 3rd expert .......for a third opinion. And then, have your onc ask each of the experts to give pros and cons for all options? Then you can meet with your oncologist and have your onc go over the pros and cons of each option. Be clear that you would like the knowledge and experience of your onc on each option. I respect the privacy of each member on the forums. I am NOT asking you/do not want you to mention your onc by name. On looking at the Lurie Comprehensive Cancer Center website, noticed the name of William Gradishar, MD who has published and spoken at national programs (sometimes on topics related to TNBC). Wonder if you onc could both present your case at the Cancer Center's review of cases conference/weekly discussion of cases where plan of care is not clear.....and/or.....discuss your case with Dr. Gradishar also asking if he would recommend someone for your onc to consult on re: your treatment plan. If ever there was a time to be your own best self-advocate it is now. Pick and choose if any of the above "feel" OK to you.......or maybe you can think of another way to approach making the decision.
With many good thoughts and gentle hugs, Grateful for today.............Judy
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dmwolf
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Posted: Aug 06 2013 at 12:38pm |
Karen1, I am so sorry you are dealing with such a difficult cancer. Please hold on to hope, as we have seen many women with aggressive, rapidly spreading cancers go into remission or long periods of stability with the right treatment. Sometimes it takes some time to figure out.
Here is my take on treatment options:
1. From what I hear, Ixempra is extremely toxic and not that efficacious for most people. Personally, I wouldn't take it, at least not in the full strength form. Maybe as a last ditch effort I would try the low dose weekly version, but only after being pretty convinced that nothing else was working. It weakens people's strength and immune systems inordinately, and really screws with quality of life.
2. Since you progressed soon after your initial treatment, which included Taxol, I wouldn't expect Halaven to be a great option. It is a drug in the same family as taxanes.
3. I am liking what I'm hearing about the PI3K inhibitor. I would give that a go in a trial if possible.
4. There are two immune modulator trials going on that I believe are very promising. They inhibit immune checkpoints, PD1 in one and CTLA4 in another. To join the trials, they check your tumor to see if it is expressing the proteins, and only admit you if the protein is present. I don't know off the top of my head the trial number, but can look it up for you (or maybe someone else knows).
5. Xeloda is pretty tolerable, and works well on skin mets in some women, so it is worth a try. Though given a choice I'd go for the PI3K inhibitor plus chemo first.
6. There are other drugs that may work for you, including Navelbine and Gemzar. Do you know whether you are BRCA+? If so, then winding your way to PARPi trial where you GET the inhibitor is a good idea. I like ABT-888 and Olaparib for BRCA mutation carriers. Inaparib used to be classified as a PARPi but has since been reclassified as mechanism unknown. It does work well for some women, though no-one has been able to predict what subgroup is most sensitive to the drug.
Good luck to you, and please know that we are with you on this road.
Much love, Denise
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DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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dmwolf
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Posted: Aug 06 2013 at 12:40pm |
Oh, and Steve would want me to insert the disclaimer that I am not an oncologist, just a fellow patient, so take any opinions of mine as just another voice from the peanut gallery.
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DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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dmwolf
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Posted: Aug 06 2013 at 12:52pm |
One more note: your experience of hearing different opinions from different specialists is unfortunately the norm. This is because there hasn't been enough research to support a convergent opinion on what to do with us, mainly because 'us' - TNBC - is a weird grab-bag of a cancer that is extremely different from ER+ breast cancer but with few unifying features other than (currently un-druggable) mutated p53. It is actually more similar to squamous cancers of the head and neck or lung than other breast cancers. It is also more similar to ovarian cancer than luminal breast cancer, though it is most similar to squamous cancers. Weird, huh? Anyways, there is lots of research going on to address our cancer, but the community has yet to find a silver bullet, if there even is one. I'm guessing one approach will never fit all TNBCs because of the diversity of the cancer. The reason I believe in immune approaches is that the best predictor for survival of untreated TNs is an immune signature. And the miraculous pCRs we hear about are almost certainly invoked by a drug-activated immune response. The problem is that if your cancer doesn't have an immune presence there, if disregulated, the immune modulators being tested now are unlikely to work. They need an 'almost functioning' system to work with and tip in the right direction. That's why they test for the presence of proteins.
Anyways, more thoughts, whatever they're worth. Keep running stuff by us as you get more information and options, and we'll help you process the onslaught.
love, d
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DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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Grateful for today
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Posted: Aug 06 2013 at 10:35pm |
Karen, You may like to consider discussing all the considerations in the above posts with your onc. On another thread, there was a link about dmwolf from the local paper which you may like to read. http://www.independentnews.com/community/article_d63c41fa-b355-11e2-a3b1-001a4bcf887a.htmlWith caring and positive thoughts, Grateful for today...........Judy
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Lee21
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Posted: Aug 06 2013 at 11:10pm |
Denise Which are the anti-PD-1 and anti-CTLA-4 trials you are referring to? I know they are being tested in advanced melanoma, renal cell carcinoma and colorectal carcinoma, but not aware of trials for breast cancer. Immunotherapy when it works can induce long lasting remission, so it is definitely a way of the future.
I have read that eribulin has activity in some cases of taxane resistance, for example, resistance due to mutations in beta-III tubulin and possibly in other types of resistance. There are also different microtubule inhibitors/stabilizers in current development specifically designed to overcome paclitaxel/docetaxel resistance.
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12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant 1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30 11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm
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Grateful for today
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Posted: Aug 07 2013 at 2:20am |
NOTE: This post is for general information only. I am posting with some general information for further discussion with one's provider on PD-1 and PD-L1 immunotherapy clinical trials, if interested/appropriate. I am not suggesting and not recommending PD-1 immunotherapy. Denise, You mentioned " It(TNBC) is actually more similar to squamous cancers of the head and neck or lung than other breast cancers. It is also more similar to ovarian cancer than luminal breast cancer, though it is most similar to squamous cancers." Have heard and read of some TNBC having similarities to ovarian cancers but not to squamous cancers of the head and neck or lung. Any good references on this? Had been trying to find out more about PD-1 and PD-L1 targeted immunotherapy before posting on this. Having mentioned PD-1, would you or anyone have a good reference article on this. It seems 3 major drug companies are in a race to develop the best PD-1/PD-L1 drug. Bristol-Myers: Nivolumab Merck: Lambrolizumab MK 3475 Genentech/Roche: MPDL3280A It seems the PD-1 targeted immunotherapy got a lot of attention at the 2013 ASCO Meeting. I have been hesitant to post on this as info seemed to be in the "Business" section of newspapers (and sure elsewhere but haven't found a good article.) Note: Not scientific journals. Newspapers. http://www.nytimes.com/2013/06/03/business/merck-has-strong-results-in-a-cancer-drug-trial.html?_r=1& Just realized the above newspaper link had a NEJM abstract link: http://www.nejm.org/doi/full/10.1056/NEJMoa1305133 http://www.nytimes.com/2013/05/16/business/melanoma-treatment-harnesses-immune-system-to-combat-cancer-cells.htmlPD-1 Clinical Trial Study of MK-3475 in Participants With Advanced Solid Tumors (MK-3475-012) NCT01848834 Phase I Trial. This study is being done to investigate the safety, tolerability and anti-tumor activity of MK-3475 in participants with advanced TRIPLE NEGATIVE BREAST CANCER (TNBC), advanced head and neck cancer, or advanced urothelial cancer. Trial locations: Chicago, Ill. Tampa, FL. Boston, MA. Phil, PA. Seatatle, WA. http://clinicaltrials.gov/ct2/show/NCT01848834?term=MK+3475&rank=4 ( "Interesting in light of what was said above of: It(TNBC) is actually more similar to squamous cancers of the head and neck or lung than other breast cancers." ) Denise or others: Are the 2 following trials CTLA-4 clinlical trials that would include breast cancer? - NCT01375842 Phase I Clinical Trial Study of the Safety and Pharmacokinetics of MPDL3280A Administered Intravenously As a Single Agent to Patients With Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies http://clinicaltrials.gov/ct2/show/NCT01375842?term=MPDL3280A&rank=5- NCT01633970 Phase I Clinical Trial. A Study of MPDL3280A in Combination With Avastin (Bevacizumab) or With Avastin Plus FOLFOX in Patients With Advanced Solid Tumors http://clinicaltrials.gov/ct2/show/NCT01633970?term=MPDL3280A&rank=2Other members, please correct any of the above if/as needed. Thanks. Grateful for today.................Judy
Edited by Grateful for today - Aug 07 2013 at 2:27am
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Lee21
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Posted: Aug 07 2013 at 12:11pm |
There are at least 3 molecules that play a role in immunotherapy currently being targeted: 1. PD-1 (programmed death-1) receptor expressed on cytotoxic T-cells, a checkpoint receptor 2. PD-L1 (programmed death ligand-1) expressed on some tumor cells and tumor-associated fibroblasts, as well as normal tissues including lymphocytes, dendritic cells and macrophages. PD-L1 is also known as B7-H1 or CD274 3. CTLA4 (cytotoxic T lymphocyte antigen 4) receptor expressed on T cells, also a checkpoint receptor
These are being referred to as immune checkpoint blockade therapies.
Monoclonal antibodies targeting PD-1 : Nivolumab, Lambrolizumab (MK 3475) as mentioned by Judy PD-L1: MPDL3280A CTLA4: Yervoy/ipilimumab/MDX-010 (all referring to the same molecule)
ipilimumab (anti-CTLA4) therapy in breast cancer: NCT01502592 - currently recruiting for early BC NCT00083278 - completed, for stage IV BC NCT00060372 - completed, for many different types of cancers
A phase 1 trial combining anti-PD-1 and anti-PD-L1 in advanced melanoma appears to lead to rapid and significant responses.
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12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant 1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30 11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm
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Lee21
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Posted: Aug 07 2013 at 12:17pm |
Meant to say:
A phase 1 trial combining anti-PD-1 and anti-CTLA4 in advanced melanoma appears to lead to rapid and significant responses.
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12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant 1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30 11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm
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karen1
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Posted: Aug 09 2013 at 11:57pm |
Thanks all for your support and great info. I have started xeloda and avastin this week. Doctor wanted to get me started on something as I investigate trials for next step. Also, my lung tumors are too small to participate in many trials (largest is 6mm). Hopefully they wont get any bigger but most trials wont accept smaller than 10mm!
Having my tumor tested for PI3 for various inhibitor trials that require this ahead of time and testing for receptors for 2 antibody trials going on at U of Chicago (one is the PD1 trial mentioned above by Lee21). A lot of new and interesting drugs out there. Lets pray one of them is the targeted therapy we all need!
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DX age 40 and pregnant with 3rd child 9/12. TNBC Stage IIIC, ACT, MX, 10/19 lymph nodes. 35 Rads, Cisplatin/Parp Trial (no parp) completed 5/13, Skin and lung mets 7/13. on Xeloda/Avastin
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Grateful for today
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Posted: Oct 02 2013 at 12:09am |
Karen,
Wanted to send some caring and good thoughts your way.
And hoping you and your treatment team have a good plan, Grateful for today...............Judy
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