Fast Tracking Regorafenib

[Ashlee H.]

Someone posted about Regorafenib being fast tracked for Colon Cancer. Guess the Phase 3 studies went extremely well- they shut it down early and everyone got to go on it. Anyone out there have any more information on this drug? How long does it take to "Fast TracK' a drug through the FDA? Is this something everyone outside the USA will have before we have? News about a new drug for us is one of the reasons I still fight and put myself through the chemo, even when I just want to stop everything and enjoy life without poison in my system.
-Ashlee

[Gaelen]

Ashlee - an FDA fast track can take as few as three months and as long as a full year, depending on how fast the company gets all of the study paperwork in to the FDA, and how grave the need, and how quickly the company can ramp up into full-scale production earlier than planned. Don't underestimate that last one - if it became generally available tomorrow, they'd need to potentially be able to supply the drug to thousands of refractory stage IV patients. That's a heckuva lot more drug to manufacture than would be used by 750 study participants - and after manufacture, it would have to be purified, assayed, and put into safe packaging (and the FDA has to approve the packaging and label content, too.)

When BMS got Videx fast-tracked...similar situation, people on the Videx arm of the Phase III study did so well that the trial was ended earlier and the drug was compassionately released to all participants in the study...BMS already had a lot of its ducks in a row on the reporting and packaging end. They'd been scaling up production for a few months so that they could be ready. Videx (didanosine) was, at the time, the ONLY alternative to AZT that was available. The need (especially in Africa and Haiti) was dramatically grave because Videx was oral, and AZT had to be given by IV. So, within three months, not only could the control study participants have the drug, but the World Health Organization agreed that it was ok for BMS to distribute them as needed in countries where the need was greatest.

HOWEVER - here in the states, even though Videx had fast-track FDA approval, it did take some time (I don't remember exactly, but at least six months) for the insurance companies to move Videx from the "experimental" list of drugs and begin to regularly approve it...and then, only for patients for whom AZT had failed. So someone whose T cells were hanging in there on AZT couldn't get Videx in the beginning, and for several months after it was considered "approved." They could get it on compassionate release from the BMS program, but without that program, they wouldn't have been able to afford the drug because insurance wouldn't cover it.

And I gotta tell you, when BMS got that fast track approval, and was finally able to ship US docs the first bottles of Videx, we had the biggest damn party you have ever seen. I couldn't even estimate how many hours I spent in haz-mat style gown up testing that drug. The overtime I put in on that drug and Taxol is the reason my condo is paid off. It was YEARS of work to get both of those drugs to fast-track status. Fast-track status for a drug is the equivalent of the "overnight success" of a performer who has been working his/her tail off in dive bars for a decade.

With regorafenib, the first patients who will be eligible to get it may have to fight for approval of the drug with their insurance companies, AND the only patients eligible for it will be those people whose cancer has progressed on all other drug regimens.

Supposedly, the report is supposed to be in to the FDA by the end of the year. They have either 30 or 45 days to act on the fast-track approval status of the drug. Meanwhile, the pharmaceutical company has to ramp up production, have that production FDA-inspected, design packaging and a label that the FDA approves, and get prepped to produce and distribute the drug. And delays by either party at any point along the way mean it will take longer to get the drug into the hands of docs who can prescribe it to patients.

I want it approved, too...but the reality of the process tells me mid-year, 2012, and then probably only for completely refractory (chemo resistant) patients who have no other options...and those patients will likely have to go hand to hand with their insurance companies to get the drug covered if they're approved to receive it.

Don't get me wrong - I'm over the moon when progress is made with new drugs and treatments. But over 20 years in pre-clinical drug testing has reinforced that the process of getting that new drugs into full distribution is NOT an instant gratification kinda thing.

[Gaelen]

Well, the specific results of the Phase III clinical trial are now released, and Dr. Axel Grothey from Mayo, the co-principal investigator of the trial, will present them on Jan 21 at the ASCO Gastrointestinal Cancers Symposium.

But I gotta tell you...statistically significant or not, 700+ person trial or not, I'm a little underwhelmed by these results. Stage IV patients on Regorafenib who had already failed all other chemos gained, median, about 1.4 months of increased overall survival and about a week of progression-free survival over patients who were taking only placebo and best-supportive-care (in this case, symptom management and treatment but no treatment expected to change the course of their disease.)

A month? A week? At the same time as being very likely to suffer significant grades of reportable side effects?

I am one of those stage IV patients who is now allergic to oxaliplatin and irinotecan, and developing sensitivities to Erbitux which may limit how much longer I can use it. That's pretty much it for chemo combination options for me. I need a new drug; we all do. But at some point, I do think patients are completely justified in asking "what is more life and time worth?" Is it worth being bedridden by side effects?

I don't think so. I don't think it's wrong to decline side effect hell just to try to parse out a few days or weeks more time. YMMV.

I do hope that the phase II clinical trial of Regorafenib, where it's introduced to patients BEFORE they run out of all other treatment options, shows that the drug has even more promise if introduced earlier in the treatment protocols.

But at this moment, I just really wanted more from this trial...and I'm not that encouraged by what I've read so far.

[Ashlee H.]

Gaelen - Thanks for the update. I had high hopes because once the FOLFIRI stops working for me, I'm out of options. I agree with you about the quality of life decision. My ONC and I always debate Avastin. He want me to give it a go again, and I'd rather die from other cancer related issues than problems I could get from Avastin, combined with Coumadin issues. And Avastin, like Regorafenib doesn't really buy you that much more time. I doubt very much "the cure" will occur in my lifetime. I know I'm living on borrowed time. I hope I can be as brave as so many who decide to stop treatment and enjoy what life they had left. My two trips to the ER last year made me realize I will be ready when my time comes.

[Fede]

I am one of those stage IV patients who is now allergic to oxaliplatin and irinotecan, and developing sensitivities to Erbitux which may limit how much longer I can use it. That's pretty much it for chemo combination options for me. I need a new drug; we all do. But at some point, I do think patients are completely justified in asking "what is more life and time worth?" Is it worth being bedridden by side effects? MY ANSWER WOULD BE "NO" ...

REALLY GREAT AND DIFFICULT QUESTION, but the question could have other response... would be Time... why? because while researcher advance in new treatments you can "win" time, for a better future quality of life...

I don't think so. I don't think it's wrong to decline side effect hell just to try to parse out a few days or weeks more time. YMMV.

I do hope that the phase II clinical trial of Regorafenib, where it's introduced to patients BEFORE they run out of all other treatment options, shows that the drug has even more promise if introduced earlier in the treatment protocols.

But at this moment, I just really wanted more from this trial...and I'm not that encouraged by what I've read so far.

I have not enough information about the latest trials treatments, but what about the latest advance in immunotherapies? I m investigating about this topic. I have seen really good results in many cases but I believe this is an awful disease without borders, and if you want I can give you the links, but of course are countries as Cuba and Venezuela where Americans perhaps have their own ideas.
I think whatever I can get the cure or a better treatment It serves us, don t care where is the location.

I hope the best for all of us.

A kiss for both

Fede

[frances]

Hi Ashlee,
This was a good question today - I saw the Jan 17 LATimes report on this and was looking at trials around the place, knowing of course the trial was ceased due to ethical grounds (as explained by Gaelen). Thanks Gaelen for noting the 1.4 month issue as pretty minimal.
However, perhaps it will go into other kinds of trials in future. I mean of course it will.
Fede, I would like to see your links!!

frances

[Badgerbuddy]

Ashlee,

I feel the same way. I am also a lymph-noder. I have two small children and of course I will take treatment until my body can't take it anymore. Last week my onc told me there is a new drug similar to Avastin, but I don't know any details.

[Gaelen]

The abstract for the CORRECT trial's oral abstract presentation and poster session at ASCO's SF Gastrointestinal Cancers Symposium is up now on ASCO's site, for any who'd like to read it.

[Fede]

Hi Ashlee,
This was a good question today - I saw the Jan 17 LATimes report on this and was looking at trials around the place, knowing of course the trial was ceased due to ethical grounds (as explained by Gaelen). Thanks Gaelen for noting the 1.4 month issue as pretty minimal.
However, perhaps it will go into other kinds of trials in future. I mean of course it will.
Fede, I would like to see your links!!

frances

Hi, Frances my workleader focusgroup...

I will give you the links:

This is the laboratory wich produce the blue scorpion poison, was used by the richest Argentine t.v starts

http://www.labiofam.cu/contactos_labiofam

The second is related to one of the key for me "IMMUNOTHERATY" was discovered by the M.D Jacinto Convit from Venezuela who discovered the leprasy vaccine, actually working with 99 years old.

http://ht.ly/8lBM3

and the institute is of biomedicine located in Caracas have importants advances in IMMUNOTHERAPY AGAINST CANCER.

http://www.biomedicina.org.ve

They could be part of our analysis.

A huge hug for you

Fede

A CURE NOT HAVE BORDERS, A DISEASE JOINT PEOPLE

[SkiFletch]

So the take home on Regoarafenib is that it's statistically a LITTLE better than other treatments for those who are out of options. And we don't yet know if it's better than other standard protocols (folfox/folfiri/etc) as a first/early line therapy. Baby steps huh?

[Gaelen]

Very baby steps, Fletch...and maybe a few pratfalls along the way...and all this study demonstrated was that it was statistically better than a placebo, not any of the standard treatments. I don't think it's been compared head-to-head against the established treatments...that may be an arm of the Phase II trial now enrolling.

I'd really like them to finish enrolling the Phase II trial where they're using it earlier in dx, with an arm for both folfox + regorafenib and folfiri + regorafenib, AND they're including KRAS mutant patients to see if they respond differently from KRAS wt patients.

Dr. Grothey's presentation (I hear through the grapevine) is going to focus on the hazard ratios in the abstract. I agree that hazard ratios are a better evaluative stat than OS and PFS, but the HR in the abstract have to be weighed against so many variables in the study report that my head hurts.

I'd love for these baby steps to be much, much bigger. Waiting for access to the full report, the phase II study, and some more information, thought.

[minolfa]

I think Sorafenib is very similar to Regorafenib and some colon cancer patients
have already got Sorafenib.

[minolfa]

hi Fede
please have you first hand info about Dr.Fuad Lechin's neuroimmunomodulation approach
to cancer?He is professor c/O Central University of VenezuelA
MANY THANKS
MYRTA from Italy
caregiver to husband stage III cc

[Laurettas]

Fede, have you found any information about the doctor in Venezuela? Is this true? We have friends down there so I will ask them if they know anything. Please post if you find out any information.

[Gaelen]

Found out a little more on the ETA for regorafenib today. My onc and i were talking , and the plan is that it goes in to expanded release sometime in April. Clinics wh want to be in the expanded release program have to apply, and stage IV patients who want the drug may need to be willing to travel to a designated clinic to get it. No idea how many clinics wrll be approved. Or where they'jj be kocated.

But if you want this dtug, you need to get your onc to apply for the expanded release program NOW.