What can we do about the delay of TDM-1

Barbara H. · 09-04-2010, 05:51 PM

Hi Everyone,
I spoke to my oncologist and obviously he is not in a position to get this decision reversed. He is quite upset with the decision because metastatic HER2 patients who have been waiting for the drug are going to die. In fact, there were a number of patients who were scheduled to receive it next week through the expanded access program that will be denied that opportunity.

The reason for the denial is ludicrous. Why would a HER2 cancer patient choose to take awful chemo treatments when more effective target therapies are available? Although the members of the FDA have medical backgrounds, they are not necessarily oncologists, and presumably do not understand the ramifications of the decision they made considering the track record of TDM-1. Obviously, they do not realize the number of patients who will die as a result of their decision.

As many of you know, I was on a phase 1 trial of TDM-1 for two years and it was a miracle drug for me. This drug did not stop working, but I developed lung inflammation. That does still not mean I couldn't try it again in the future.

I am not writing on behalf of myself. It pains me to know that many of you are being denied access to this treatment.

Apparently this decision can be reversed if many of us write and voice our opinions and experiences. The FDA needs to understand why this drug needs to be approved ASAP. They need to know about the number of patients who will lose their lives if they do not reverse this decision. They need to understand their responsibility for these patients.

Unfortunately, I do not have experience being an advocate and do not even know how to get this message out so that the essential people read it. For example, President Obama's 60, 000 letters he receives each day are screened by readers that decide which ten letters he will read on that day. I am also not sure to whom we should send our letters. My oncologist will hopefully let me know if the advocates at the Dana Farber have any ideas.

Please post any suggestions or ideas you may have about this critical situation. Remember, we may be able to make an impact if many of us write.

Thanks for reading and thinking about this issue.

Kind regards,
Barbara Holz

Jackie07 · 09-04-2010, 06:02 PM

Well, Health Care Reform has been a hot topic. I'm sure our e-mails to the White House will get some kind of attention. President Obama's Mother died of a gynecological cancer and their experience with her insurance company was a traumatic one.

Let's get on with it!

www.WhiteHouse.gov

Nancy L · 09-04-2010, 08:17 PM

I do not believe Obama cares in the least about this decision. This is the start of what Obamacare is all about.

I get disgusted every time I hear him say how hard it was for him to watch his mother argue with insurance companies. I say, Where was he? He was a grown man with a law degree and the one who should have been arguing and then maybe he would understand our plight. I took care of these issues for my mother and my sister when they were ill. This is what family does when they truly care. I think he is a phony.

ElaineM · 09-04-2010, 08:59 PM

Maybe finding out who the "movers and shakers" at the FDA are and writing to them is a good idea. I think every president has a staff that decides which pieces of mail he sees and what he doesn't.

Chelee · 09-04-2010, 11:51 PM

Barbara,
I would love to do something about this T-DM1 nightmare. Sign me up...lets do whatever it takes to be heard. Waiting till 2012 is unacceptable! There are so many women that were depending on this drug...myself included. We need to find a way to get the ball rolling--so lets all put our heads together and be as pro-active as possible.

Nancy...AMEN to everything you said...I couldn't of said it better myself! I'm not sure who we need to direct our letters too...but I do not believe for one minute it's the White House. Now Elaine might be on to something? The FDA might be one good place to start. Lets figure this out and get going on it...T-DM1 has already proven to be a life saver so we need to make sure it's available to all that need it asap. Any other ideas on who we write too please jump in here. (Thanks Barbara for bringing this issue back up to the top.)

Chelee

Pam P · 09-05-2010, 05:16 AM

In honor of Joe's memory and work, please let's not let this discussion get into political views for or against Obama etc. Let's just focus on the best ways to help accomplish our goal of getting tdm1 to people who need it. I'm going to send an email to the white house link right now and I'll also send letters to others if any of you come up with names/ addresses within the FDA or other influentials. I don't have the advocacy or research expertise but I can write letters.

schoonder · 09-05-2010, 07:00 AM

If Roche files for T-DM1 approval by mid-2012 using Emilia's trial results, then earliest approval for this drug would be onset of 2013.

How about Congressional FDA Oversight Committee for those letters?

FDA refused to look at "any" of T-DM1's trial results because Roche failed to include "all possible" mbc therapies in this trial.
Since T-DM1 a "targeted" therapy has shown to be an effective treatment against HER2+ cancers, extending this trial, looking for candidates that failed those other "much less effective", thus "much less prescribed" treatment options, would've been a "waste of time".
However the FDA, overly risk averse, opted to use this omission, one that really had no bearing on trial outcome of HER2+ candidates, to issue a Refusal To File (RTF) letter. This RTF will delay approval of this very promising drug by at least two years.

Barbara H. · 09-05-2010, 07:06 AM

Thank you to all who have responded. I agree with Pam that in Joe's honor as well as considering the purpose of this website that we should not discuss politics. My purpose for starting this thread is to try to get this decision reversed. I will also write a letter, but I was hoping for ideas about how we can get our letters noticed. I also hope to be considerate about not putting down the FDA. However, I just do not understand how they could have rejected T-DM1.
Hopefully, we can change this decision.
Barbara H.

Barbara H. · 09-05-2010, 07:13 AM

Schoonder's reply is absolutely correct. FDA's refusal was based on the technicality that she describes. Their decision is shortening lives and the quality of the lives of HER2 patients that need it.
Barbara H.

Sheila · 09-05-2010, 09:03 AM

I agree, we need to do all we can...too many of us cannot wait until 2012 or 2013 to get this drug. I was ahead of my time for the Herceptin in the adjuvant setting, it was only for stage IV when I was diagnosed. Now, I am stage IV, running out of options, and still unable to get the TDM-1... Does the FDA really think it matters when we have nothing else to try?
If they were in our shoes.............

hutchibk · 09-05-2010, 10:40 AM

The hopefully 'fatal flaw' in their written decision was the sentence "regardless of HER2 status" ~ you can't approach efficacy of potential new treatments for HER2 cancer from a "regardless of HER2 status" standpoint... IT IS ALL ABOUT THE HER2 STATUS. That is why they are developing these targeted treatments, because if the other available treatments that "have not been exhausted by the study patient population, regardless of HER2 status" worked for us, then there would be no need for intense research and focus on treating this subgroup. It's sounding like a "one size fits all" mindset that is so scary in the bigger picture.

Chrisy knows the woman at Genentech that Joe was very close to... perhaps she can connect us with lobbying folks who know the inner workings of this insane bureaucracy and we can offer our powerful, survivor/patient voice to a coordinated push for the FDA to reconsider their flawed thinking.

As well, if anyone has meaningful connections to Komen, they are the most powerful lobbying group for breast cancer and they are currently applying a full court press in coordination with Genentech to the FDA about Avastin... I am guessing if we hit them with our outrage about this, they would be very interested in helping, if they aren't already in the early stages of it.

Anyone here close to Komen? Or does anyone have an in to Nancy Brinker?

ElaineM · 09-05-2010, 11:01 AM

Yes. We need to do something that will help all her2 positive people and honor Joe, but still not be too political.
Sorry I mentioned the White House, but I have personal experience with important requests not getting through to the president in a timely manner. I don't think it is President Obama's fault. He is a very busy person and can't take care of every e-mail request personally. He probably gets hundreds every day. His staff may be in a position to decide what he sees and what he doesn't.
I will go to the FDA website to see if I can find out where we can send something to.

Debbie L. · 09-05-2010, 11:56 AM

Good luck at the FDA site, Elaine. I just spent a LONG time there and couldn't find anything. They started this big "transparency" initiative and if there's anything there about TDM-1 or about inviting public input, it's opaque, not transparent. Jeeze.

They do have a blog about their transparency initiative, where comments can be posted. I wonder if that might be a way to get their attention. Although the ruling on TDM-1, as I understand it, is a done deal - it's not like Avastin where they still have the final meeting coming up.

So here's the blog page if anyone wants to try there:
http://fdatransparencyblog.fda.gov/

The other thing I noticed, while googling all over the place for news of some organized reaction to the TDM-1 accelerated approval denial, was that posts here on the HER2 list show up in a google search. Isn't there a way to make forums private? I'm on several others that don't show up in google.

Debbie Laxague

hutchibk · 09-05-2010, 12:02 PM

Elizabeth Thompson, Senior Vice President of Medical and Scientific Affairs for Susan G. Komen for the Cure.

5005 LBJ Freeway, Suite 250 Dallas, TX 75244
1-877 GO KOMEN

She is the one quoted about Komen's reaction to the FDA/Avastin situation.

Perhaps we can write her a letter outlining our concerns and see what their position is... see if there is any help they can offer.

I don't have time right now to start a letter, but I can certainly contribute to it.

Rich66 · 09-05-2010, 12:08 PM

Brenda,
I like your ideas on identifying larger entities/avenues to force the message through.
Another powerful avenue might be news organizations. We saw how media picked up on Herceptin years ago. Regardless of political spectrum, health care issues are hot now in terms of getting viewership or readers. Getting a few TDM1 success story patients in front of cameras..maybe picketing in front of FDA headquarters with a media notification could be powerful. I see some of that with Avastin now.

Regarding google searching, I think having forum topics searchable enhances information access. If concerned over privacy, maybe it means being more discreet with names and e-mails in profiles.

ElaineM · 09-05-2010, 12:15 PM

Good idea Brenda. I just did a search for "writing to the FDA". Here is what I found so far. I am still checking and might find more later.
http://www.fda.gov/AboutFDA/ContactFDA/default.htm
Please see the left side bar, right side bar, middle employee directory, FDA centers and offices and other information you might be interested in searching.
Even if the TDM1 decision is a done deal we may wish to comment on it as consumers of health care. It might be good for the FDA to hear from consumers once in awhile since FDA decisions may affect our health care. I do not think this is political. The FDA is an agency that is supposed to advocate for us as consumers by checking the safety of the products we use and the medicines we take.

ElaineM · 09-05-2010, 12:20 PM

I like your contacting the media idea Rich. We have to pick a good one if we want to do that though. Some of us may not want to be in the spotlight. I am one of those. I am better at behind the scenes work. What about writing to some oncology organizations? Is that a good idea? Going back and reviewing how Herceptin and Tykerb got approved might help us get some ideas too.

Emelie B · 09-05-2010, 12:34 PM

I like all the ideas. I think we should at least start a petition type thread and we can all sign it and possibly print it and send to whomever we think would help assist us. I would be glad to do whatever I can.
I also think we Rich's idea of media is excellent. With all the c--- I see on the morning shows, our issue would surely enlighten someone who needs this drug too.
My daughter lives in D.C. and I can always go visit her and try to do something there.
Let's get this thing rolling!!!!

ElaineM · 09-05-2010, 12:39 PM

All the ideas are good. See what we can do when we put our heads together !!
One more idea. We could team up with another organization like Susan Komen or others and do something.
By the way, "Stand Up To Cancer" will be airing on most of the T. V. channels on September 10th. That is a program about raising money and awareness for cancer research. I think they have a website. Should we look around there for ideas?

schoonder · 09-05-2010, 01:25 PM

What might have lead Genentech astray.

Was omission of certain non-HER2+ therapies in their T-DM1 trial design a glaring oversight by Genentech that compelled FDA’s RTF response, or was this a misunderstanding by Genentech attributable to lack of specificity by FDA during preceding trial discussions?

Did FDA’s acceptance of trial requirements that did end up receiving Accelerated Drug Approval mislead Genentech in T-DM1's trial construct?
Case in point a recent accelerated approval ruling re: Tykerb where, according to FDA Tykerb WAS NOT compared to Trastuzumab-containing chemo regimen for treatment of MBC. This compare could be done later, why not allow Genentech to correct their shortcoming in the "compassionate" trial setting?
FDA approves TykerbR for use with letrozole to treat certain postmenopausal women with hormone receptor positive metastatic breast cancer

On January 29, 2010, the U.S. Food and Drug Administration granted accelerated approval to lapatinib tablets (Tykerb®, GlaxoSmithKline) for use in combination with letrozole (Femara®, Novartis Pharmaceuticals Corp.) for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that overexpresses the HER2 receptor and for whom hormonal therapy is indicated. Lapatinib, in combination with an aromatase inhibitor, has not been compared to a trastuzumab-containing chemotherapy regimen for the treatment of metastatic breast cancer. The approval was based on a clinically meaningful increase in progression-free survival (PFS) observed in a single trial (EGF30008). As a condition of accelerated approval, subsequent randomized trials are required to verify and describe the clinical benefit of lapatinib in patients with metastatic breast cancer who have received prior treatment with trastuzumab.

EGF30008 was multinational, randomized, placebo-controlled trial of lapatinib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive metastatic breast cancer who had not received prior therapy for metastatic disease. Patients were randomly assigned to receive lapatinib (1,500 mg once daily) plus letrozole (2.5 mg once daily) or to placebo plus letrozole (2.5 mg once daily). There were 219 patients (17%) who were HER2-positive, 952 (74%) patients who were HER2-negative, and 115 (9%) patients did not have their HER2-receptor status confirmed.

Accelerated approval was based on the results from the group of postmenopausal women with metastatic breast cancer that overexpressed the HER2 receptor. The primary efficacy endpoint was PFS, defined as the time interval between randomization date and the date of either first documented disease progression or death due to any cause. The lapatinib plus letrozole combination had a median PFS of 35.4 weeks compared to 13.0 weeks for the placebo plus letrozole arm (HR = 0.71, p = 0.019). The overall survival data are not mature at this time.

Safety data was evaluated in 1278 postmenopausal women with hormone receptor-positive metastatic breast cancer. The safety profile of lapatinib in this trial population was consistent with previous safety data. The most common adverse reactions (=10%) in the lapatinib plus letrozole arm were diarrhea, rash, nausea, and fatigue. Elevated liver enzymes and bilirubin were reported in 53% and 22% of the patients receiving lapatinib, respectively. Among 654 patients who received the lapatinib plus letrozole treatment, 26 patients experienced Grade 1 or 2, and 6 patients experienced Grade 3 or 4 decreases in left ventricular ejection fraction.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available on the FDA website.

http://www.asco.org/ASCOv2/Practice+&+Guidelines/Practice+Management+&+Reimbursement/FDA+Drug+Alerts/FDA+approves+TykerbR+for+use+with+letrozole+to+tre at+certain+postmenopausal+women+with+hormone+recep tor+positive+metastatic+breast+cancer
Roche surely isn't shirking their responsibility in completing evaluating T-DM1, presently company is conducting two large, international MBC phase III trials. The issue is that, what appears to be a minor technicality, an inconsistent ruling by FDA, is keeping this drug for at least two years out of hands of critically sick people, of which a good many no longer have viable options for efficacious treatment on hand.