news from ASCO-- some joyous, some a downer--may set things back a bit
 

The last few ASCOs and San Antonios I have been hearing about the "overabundance of riches" of numbers of drugs approved and available for her2+ breast cancer How could there EVER be too many!

YESTERDAY, , there was a talk by Edith Perez on how helpful herceptin is in T1abc No patients-- hardly anyone treated with chemo and herceptin recurred.(which is why it took so long to come up with that result)

Today, Martine Piccart reported the first findings from the ALTO study. Neo ALTO had previously been reported (I SEEM TO THINK THAT WAS @ SABCS) and had fabulous results regarding how many more pCRs there were with neoadjuvant dual her2 blockade.

Today's report was of adding lapatinib to herceptin ADJUVANTLY, not neoadjuvantly, and there was no real statistically significant improvement found by adding lapatinib to herceptin adjuvantly, but lots of side effects (mostly rash and diarrhea as many of you here have noted)

The reason today was a downer is that George Sledge followed Dr. Piccart on the podium and presented the summary/editorial about what it all meant and then later on there was further discussion in a
postplenary"session. On both occasions, he and others generalized (perhaps overgeneralized) that this was likely going to be the early "end" of the FDA's new policy of approving new drugs based on pCR results in neoadjuvant trials(as occured with pertuzumab), without requiring the thousands of patients and tens of years required to produce a successful adjuvant trial.

Already they were talking of giving up on pushing dual her2blockade into the adjuvant arena eg, pertuzumab+ herceptin, and although Martine Piccart said instead of trying to find new and better antiher2 drugs and combinations, perhpas they should be turning their efforts to trying to discover if there is a subset of patients who do not need chemo in addition to her2 therapy.



It has sounded to me in the last year and a half or so as if the clinical researchers were no longer as "excited" by the prospect of "curing" her2+ bc or at least turning it into a chronic treatable disease and would be turning their interest and efforts elsewhere. While I wish they could get as remarkable results with triple negative breast cancer, we are still losing way too many to this disease which needs more drugs, more combos and better biomarkers, pathway elucidation, and understanding of its "Achilles heel" as well needing to be further subdivided into many more subsubtypes in order to be divided and conquered.

My sense is that their earlier resolve to do better may be being tempered by their fear the cost of treating with two or more exhorbitantly expensive drugs and what it will mean for healthcare finances.**

Perhaps it will turn out that immune therapies like adoptive Tcell therapy will turn out to be more effective (although probably not cheaper) than multiple targeted agents. I just hate to see people turn so negative so quickly, when
the need for better solutions is so great.

**All the more reason to start testing for disseminated tumor cells (via bone marrow testing) -- perhaps treating only those with dtcs with combination therapy or other expensive regimens will save both money, lives, likelihood of producing second cancers, cognitive deficits, early aging from nontargeted agents etc

I, myself, interpreted Dr. Piccart's paper differently--that it showed that herceptin's action through ADCC (the immune system) was far more important and difficult to
become resistant to than just her2 receptor blockade/inhibiting of the tyrosine kinase (as lapatinib did) and that enhancing the ADCC or working via interruption of cell cycle (as Y. Yarden recommends) would be more efficacious.

I was saddened by the news on Barb tonight and remembered that after hearing this paper and the comments it spawned, I wanted tp give a peptalk to the young researchers standing by their posters so they would come up with the "latest and greatest" However there was no poster session this afternoon. In fact there seems to be more drug company "real estate" in the Chicago McCormick Place convention center and less for posters at this year's ASCO (as compared to previous meetings) with less poster presenters standing by their posters, as well.

It is a still a fabulous conference and there were lots of very exciting talks on many different cancers---just not particularly her2+ bc.




There were a lot of remarkable things to report on (and I hope to when I am more rested), but her2 was not the star it was at SABCs or previous ASCOs I am sorry to report. Still another day and a half until the meeting ends, though

Off to get some shut-eye!

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Thanks Lani - a mixed bag of news indeed. Many people here are putting a lot of emphasis on the immune therapies and molecular profiling, but i agree we need people looking for a CURE!
Best wishes... Pam

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Lani - is there anywhere their presentation will be available to us? I am curious about the logic. I am a little resentful that the medical community feels the financial cost is too much to extend some lives. We're worth it! From my understanding the progress made by obtaining pCR in neoadjuvant treatments is having a great effect on DFS and OS. Is the data in Phase IV not showing this for Perjeta?

While I wholeheartedly agree we need to determine the subsets that can avoid chemotherapy - logic tells me we can work on determining other subgroups who need combined therapies to stay NED simultaneously.

I don't agree with the current system. It is broken. Any system that allows people to die to prove that something works is a terrible system. I'm offended that the FDA would go backwards after the progress with the quick approval of Perjeta for neoadjuvant treatment.

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Thanks Lani for the information. As usual very interesting. Was sort of left hoping that Dr Slamon doesn't abandon his mission to 'cure' or at least turn her2 into a manageable long term condition. I found some notes from 4 years ago I'd made where Dr S had 'predicted' that her2 would be the first breast cancer type that nobody would die from! I hope and pray he's right and that the push for the cure continues as fervently as before!


Ellie

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Lani - any word at ASCO on the Marianne trial with T DM-1 ? I am still hopeful that many more her2 can be perhaps " cured " by earlier tx with t dm-1. I wonder what Lorraines' response would have been in 2006 - at initial dx. with stage iv but only one visible tumor in liver - no more progression ? - no TAC, no tyk/xel., nav., gem. , carbo , abraxane, avastin, no second hair loss with adria , no stents in kidney , bile duct ...
as far as costs - we have to spend to win the War - each new drug is a step towards the Cure - even those trail drugs that " fail " as my first wifes' did - are forward steps - we don't waste time on false paths. slow , small trials and cost , no access for most - all are reasons to support the Right To Try Phase II and III drugs Law - a 2 tiered system with true compassionate use for late stage iv pts - too sick for trials . the Law has passed in Colorado and Louisiana . But we need Stage IV Activists to tell the story - too many skeptics - you pts in trials , or who have tried to get comp use - you are the real Experts - you know the System is broken . the Diane Rehm show on NPR had a whole hour show last week on the Right To Try law - all " experts " , all without actual first - hand knowledge of the real broken , biased system . Ms. Rehm had NO Stage IV trial / comp use veterans on her show - that's like having a show on AIDS Activism with out the Activists !! Speak Up !

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

I have read somewhere that only 4% of the research money go into stage iv to begin with. I hope that's not true, because for me - being 43, stage iv off the get go, with a 5 year old daughter, that is EXTREMELY scary. If we can't find a cure in my lifetime, then my "selfish self" needs the list of treatments that may slow this thing down to be as long as ever possible.

I understand, though, that stage iv BC (HER2 or any other) is not the "pink success story" that easily raises money, and is good for "sunshine" publicity a la "you'll be fine". It's painful and arduous, and a lot of time and work spent for sometimes very little gain or progress. I know it's ugly. Only: that does not help me at all, I still want to live?

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Annette - we want you to live too!

I don't know if the 4% is correct, but am so pleased that you have both Perjeta and Kadcyla to use against stage IV Her2 cancer.

I will agree the system does not work efficiently and effectively for stage IV in desperate need of controlling their disease.

However, some still benefit from the recent progress - hoping it will be you in that category.

best regards,

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

I agree - I'm lucky to be in this situation "post-Herceptin and Perjeta" - some 10 or so years ago, it was even "more scarier"... However, I find it daunting when my Onco tells me to all but stop looking at what's currently going on in research, since she feels it's unlikely I will have enough time to profit from it. Add to that that the processes seems get longer and less focused, it's bitter pill when you don't have time to loose...
Oh well, I'm still at the beginning of the journey, and yes, I currently put my hopes in first line treatment lasting for a looooong time...

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

i have to say your doc sounds like a downer - especially when she gives you such a very up to date tx regimen, the full ptoential of is not yet known but very promising. 2 biologics shuting off multiple pathways. plus a taxane chemo to clean out the weakened cancer cells. i think u should consider tx at a top research hospital, or at least a 2nd opinion. we have greeat confidence in out doc , ansd she would never , has never talked like that. after perjeta , if u even need it , comes t dm-1. it would be good if more docs would combine the 2. some do on thier own. that combo is another near future step forward. my wife is doing very well on just t dm-1. . my feeling is that t dm-1 is stronger than perj for aggressive her2 , as its a chemo and biologic. so you have it uf u need it. Farber is doing a trial on a doxil / 2 biologics ( i think herceptin and perj ) combined t dm-1 style. neratinib shows promise. other inhibitors like it are in lab studies/ trials. plus immunotherpy / oncolytic viral agents , and more in development .
We Stage IV Rights activists are doing our best to speed up this Slow FDA - led approval system . Farber has noticed an uptick in new , more effective drugs coming out since 2005. and that is putting pressure on both the FDA and pharma.
There actually is more focus on this slow FDA - and pressure is showing in their approvals - reversing the ban on iclusig, a leukemia drug, after pt. / dr. pressure ( a group of docs speaking up with thier pts was a first ! ) . and fda's granting of breakthrough status to er + drug palbociclib, now priority review for olaprib for ovarina, and more pressure will come from Us ! We Support the State by State " Right To Try " law to fix the compassionate use system . here is my wifes' testimony in favor of the law : http://youtu.be/AkQOLGpXf98. So, do not lose Hope - God Bless, and Heal !

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Hi Phil, thanks for your message!

I think the fact that the combo is so new may be part of the issue - I believe she simply does not really know what to expect since I'm her only patient with my diagnosis currently on it (not her fault of course, even though I do feel somewhat "guinea pig-ish" and not sure I'm too happy about that). There was a suggestion I should go off the current combo after the 3rd round because the sclerotic margins that had started forming around the met in the spine were considered progress...
Luckily, I have access to another onco abroad (she was involved in the trials for this combo in Germany). And my onco here contacted Princess Margret and colleagues in another hospital in Toronto to discuss her findings. The second and third opinions were opposite to the initial take - they basically said all they found is GOOD news, not bad. Wait and see - had #4 last week, there will be another check after #6.

I have heard about T-DM1, and I'm VERY happy it was such a great drug for your wife! I hope she's feeling well and going strong! It was approved in Canada as second line only a couple of weeks ago, so should I need it, I should be able to get it "the regular way". Still, I would rather get some more time out of first line, if I can...

Annette

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

I just read about Iclusig in one of my pharmacy journals.
I had no idea there was a controversy behind its approval.
That was not mentioned-interesting

Paul

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Annetchen - is your doc a breast cancer specialist ? has she txed anyone with T DM-1 ? this talk about stopping after 3 rounds sounds strange to me.
we left the suburbsd right away in 2006, left a very nice, generalist onc., nice but not in touch with the latest tx's and how to use them. so he recommended a conservative - " save strong chemos for later " approach . we had both lost spouses to cancer before - so we weren't buying it . tx aggressive stage iv cancer aggressively is our motto. so we went to a top research hospital with a bc specialist clinic - MGH in Boston . got a very experienced, specialist onc who agreed with us - if we wanted to go all out she would and we did . it paid off . i think she would have not even considered stopppuing atx with some response after 3 doses . she would complete it and try to make sure cancer is dead . unless intolerable s/e 's came up. u can see from lorraines' list of chemos up top that it was not easy , but we feel it was worth it. there are no guarantees -none of these are cure -alls , but the above strategy i think improves the chances.

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Not sure - I do know that she has other BC patients - not sure she has MBC, and definitely did not have anyone on the Herceptin / Perjeta combo - understandably so, given P. was only approved for 1st line MBC a couple of months ago in Ontario.

I have considered switching to Princess Margret (which has a large, fairly well known BC abd other research "branch"; given that, you can get early access to trials; I have also gone for molecular profiling there).

At this point, though, I figure everyone would have done what my onco did (at least the second opinion absolutely concurred) - and not having to drive downtown for every chemo is a plus when you have a 5 year old daughter.

Only, if I had not protested loudly, I might be off first line and on Kadcyla now... Also wondered whether the approach to treat fire with fire is what should be done. It's the old adage: once you're MBC, you're palliative by definition (even though years ago Hortobagy noticed that there IS some patients that are actually "cured" - for all intents and purposes). At any rate, I don't think we're making a mistake with the current first line treatment. And hope, of course, that it will keep me stable for a long time. Once that is not the case any more, we'll have to reconsider. I already wondered whether Houston would be an option...

It's all complicated... Is SO wish for my old, simple life back. Oh well, it is what it is...

Annette

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Lani,
Looking for any info on TDM-1 and Perjeta paired up. Nina has a spot on a subcarinal node and would like to try that combination. Also trying to be patient 1 for IT Perjeta at USC.

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Paul,
I did the TDM-1-Perjeta for 18 months. Some have gone much longer...three years and counting. Hope Nina is doing well, and thank you all for your research and willingness for confrontation with the FDA.
Karen

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

http://clincancerres.aacrjournals.or...-0358.full.pdf

http://www.immunogen.com/img/T-DM1%2...at%20SABCS.pdf

http://www.ncbi.nlm.nih.gov/pubmed/23783223

http://www.healio.com/hematology-onc...-breast-cancer

about to travel so don't have a lot more time just now...

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Tdm-1 is already appr. for those who have progressed on a taxane, and pert for earlier stage her2 . Mariane trial data on their combined effect shows increased response . I am not quite sure where the marianne results are in this grossly slow FDA drug approval system , but i would seek the combo from your onc. " off -protocol ' based on these results, and the slow system . if any resistance , think about going public with media , and getting your political reps involved. Good Luck and God Bless.

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

Thanks. We go try to convince people on Wednesday afternoon. I knew that there was information out there in this group. I will email how we do and when IT Perjeta will start at USC, and whether there are sub-sites at other locations.

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

the lack of full approval for perjeta is one of Our Stage IV Rights issues. at last Falls' Metastatic BC Conference at Farber , i asked about it . Farber said that This FDA " had no timetable for full approval of Perjeta ', for Stage IV. There is no sense of urgency at the top of the FDA or in the Boardroom at Big Pharma. They are far removed from Our Stage IV Reality - they pity us but do not respect us - and our Big Advocay groups don't understand or represent us . Some are in the FDA camp - BC Action is one and they sit on our bc FDA Advisory Commitee !! We need our own Stage IV Rights Advocacy Group - open to activists fighting all terminal diseases !

Re: news from ASCO-- some joyous, some a downer--may set things back a bit
 

All I can say Phil is that I am pushing as hard as I can on multiple forums. The problem is that the pharmas and doctors do want to get sued, the FDA is criticized for going too fast on failed drugs and too slow on ones that are safe, and the public does not know what they want if they are uninformed. Those of us who work to get knowledge focus on a single patient, a single issue, and often not on what can help the most people. I know that Perjeta/TDM-1 is the correct systemic for many people, but there may be other options. New clinical trials show a HER2+ treatment that had better results. So now I need to go explore that drug and its case studies. I will be an activist, but I want to not misstep in what I do so I lose any legitimacy about what I write and say. My background carries a level of importance that I cannot afford to lose any more than the doctor or big pharma can.