Sunday, November 24, 2013

If money = access to cancer care.....we have a problem!!!!

I have worked very hard all my life.  I've been employed since the summer I turned 13, when I worked five days a week for a local dentist answering the phone, handing him equipment, cleaning spittoons, sterilizing supplies, taking out the trash, and cleaning his home once a week, from toilets to linens to stripping wax and reapplying it to his hardwood floors.  All for $100.00 a week.  And I was THRILLED!!!!  Starting that summer and for all the others, including some school breaks, that followed, until I left that small south Alabama town with my Associate Degree in Nursing, earned at the local Jr. College....Jefferson Davis Junior be exact, I worked for the dentist, earning the same rate of pay, eventually learning to make dentures in his lab, saving my money.  Those earnings allowed me to fund my move to Chattanooga and start work in the big city as an RN in the local Children's Hospital...for $7.70 an hour.  I was in high cotton.  I had an apartment (albeit a tiny one!!!), paid all my own bills, and learned new things everyday.  And, yes, it has been a while back, but this was just in the mid-80's y'all!!!  I've put myself through school via scholarships and my own pay check three times.  Yes, I married a doctor, who put himself through school by working three jobs and taking student loans, which we paid off together during our marriage.  And you know what????  I am lucky and wealthy beyond measure.  Obviously rich in friends and family and life experiences, but those will not buy you cancer care.  The fact that I have been able to afford the care I have attained puts me in a small minority group.  The fact that I could pay for the trips to Tampa and the car and hotel and food it cost me while there makes me different.  I paid the deductibles, co-pays, and the out-of-pocket expenses of $800.00 every three months just for the scans, required for my trial participation, myself.  Moffitt didn't pay for those.  BMS didn't pay for any of those expenses.  How many people do you know who could afford such care?  I don't know very many.  Most of the people I work with, people I care for, my friends and family could not.  Is that right?  I don't think so.  And when you look at the video describing the imbalance of wealth below....sadly the outlook is even more bleak....

Wealth Inequality in America

So, Weber and Ribas agree (see 11/18/13 post) that if you have melanoma (or perhaps more specifically...if THEY had melanoma) you should get yourself to a top-notch melanoma cancer center.  I agree.  I did that.  But, how are most folks supposed to make that happen?  Yes, there are a number of agencies and programs that can provide at least some assistance, but that means that a sick and frightened person is going to have to have the where-with-all to find and access that.

We were all so happy that ipi was approved by the FDA.  Only to find that Weber and Ribas admit, folks are not prescribing it in their local offices or county facilities.  They haven't bothered to credential folks to do it and are not utilizing it because of cost.  They are not willing to eat the wholesale cost of $120,000 if the insurance company won't cover it or if the patients themselves fail to pay for "their portion."  Not really how we all thought this was going to roll, is it?

I don't have a ready answer. I don't know what I am going to do. Do we need a Phase IV trial for drugs AFTER they are approved to determine whether any patient can afford them???  Being diagnosed with melanoma or any other expensive and deadly disease is unfair enough.  Patients carrying that burden should not be denied access to life saving and extending drugs just because of their bank accounts. Should they? - c

Friday, November 22, 2013

Running...thoughts. Alive? Dead?

Running today I found that I was thankful.  Thankful to be running well and easy after having a cold that flared up my asthma for the past couple of weeks.  Thankful that my sweet love was also my very best friend.  That my children are people I admire.  That my daughter and I could agree to disagree about Mrs. Dalloway, "Mrs. Dalloway said she would buy the flowers herself." That she would happily entertain my notions and have such conversations with me.  That I have the very BEST PEN PAL EVER (thanks Jonathan!).  And I ran on, my thoughts turned to menus.  Tuna and soba noodles with sesame seeds, green onion and zucchini tonight.  Pork loin, dressing, green bean casserole, maybe brussies for Bentie, and gooey chocolate cake with rum soaked cherries on the side for Thanksgiving.  A blackberry syrup I need to make for the morning after's bread pudding.  Oh...and I need pumpkin for the pies.  Then, planning the sandwiches and scones with berries and cream for a perfectly British high tea in early December for a very special grad to be!!!!

But, last week, while jogging in a similarly foggy, misty, moisty late fall day here on the mountain, I was contemplating the silhouettes of the mostly bare trees.  A few were still hanging on to their brown and crumpled leaves, but most raised empty branches skyward.  With mild curiosity, I looked over at a neighbor's yard to see if the long dead tree he seems to be taking bets on as to whether it will land on his garage or the power line was still standing.  Yep.  Still there.  But looked no different from its mates.  If you hadn't watched its demise over the past seasons, you would have to look very carefully to see that it is not as viable as its fellow forest friends.  And that made me think.  Do I live like I'm alive?  Or dead?  What do my choices and actions show?  Cause, spoiler alert!!!!  We will all join my now hidden friend sooner than we can imagine.  I won't have a choice about that.  But, I do have a choice about today.  When my leaves are intact, and even when they aren' I making the most of being alive?  I've watched some choose to live their life as though dead already, allowing opportunities for joy and love and friendship to wither and dry on their branches.  I don't want to "live" like that.  I don't want to be part of the walking dead, hiding among the living.  I know that everyday may not be filled with joy and delirious happiness...but I certainly want it to be filled with life!!!  Even if slightly random, bizarrely beautiful, and chaotic!  To yours - c

Monday, November 18, 2013

Mo' Money....Mo' Bettah....Melanoma's Therapies (B-RAF, MEK, ipi, anti-PD1) and Their Cost and Availability

 Melanoma:  From Impossible to Treat to Poster Child for Targeted Therapies  Published online:  October 23, 2013. Produced by Nicole Beagin.  In September, Mark Fendrick, MD, co-editor-in-chief of The American Journal Of Managed Care, led a discussion of experts about advances in the treatment of metastatic melanoma, which examined both the promise offered by new therapies and the issues surrounding cost, payment, and delivery.

Jeffrey Weber, MD, PhD, Moffitt Cancer Center, Tampa, Florida
Antonio Ribas, MD, PhD, Johnson Comprehensive Cancer Center, Los Angeles, CA
Jennifer Malin, MD, PhD, Manager and medical director of Oncology, Well-Point

(Quoted, but edited, by me!)

Weber:  Melanoma has gone from being regarded by many oncologists as an impossible to treat and hopeless malignancy to a disease...that is the poster child for new targeted and immunologic therapies...  That being said, there are major unmet needs in our field because...we still have a pretty narrow repertoire of drugs...[with] pretty serious toxicities, and we are a long way from curing a significant proportion of our patients.

RibasHaving seen this remarkable change in a short period of a remarkable benefit to patients...but we are still faced...with many patients who are either not responding, responding for a short time and progressing, or having side effects.

Patients who were treated 2-5 years ago [with immunotherapies]...continue to respond and patients with T24 blocking antibodies, the longest...for 12 years...but we need to make it more efficient for everyone... The B-RAF inhibitors, vemurafenib...then the B-RAF that is called dabrafenib, which is a very recent approval. ....when we select patients with the B-RAF mutation, which is around 50% of melanomas, we are close to guaranteed to have some...patient benefit.

Over 80% of patients have some shrinkage of disease....but the majority - not all of them, but the majority - will progress...and the median duration of response is around 6-7 months, although there are some patients from the Phase 1 trial of vemurafenib who are now going beyond 4 years and are continuing to respond, but that is the minority.

These are targeted therapies that block the driver oncogene which leads to cell cycle arrest and response in the majority of patients... Around two-thirds of the progression mechanisms go through reactivation of the same pathway and a signal through an immediate downstream, a factor which is called MEK, which is a kinase under B-RAF... Then we have the MEK inhibitor trametinib that has been approved to use as a single agent in B-RAF mutant melanoma. But that is not where we are going to be using it because by itself, trametinib is less effective...and more toxic, so it is probably one of the only approvals by the FDA that we know from the start that we are not going to be using in the way the current label is written.  You can use it in combination with the B-RAF inhibitor and you can use it in patients who progress on the B-RAF inhibitor because there is actually no activity there. But there is a lot of activity when you put it together, is one of the examples that I...know in medicine where you have 2 effective drugs, that you put them together and they are not only more effective but they are less toxic...which should impact on the cost-benefit ratio because even though...2 drugs are more expensive than 1, the side effects are decreased and the benefits of the drugs is markedly improved...  I think most of us would agree that this will be a drug that is cost-effective.

Weber:  I think everyone agrees...the expectation certainly is that the Phase II study results...with those 2 drugs are going to show serious benefit and major prolongation of survival, but again we don't have the data and they won't be out probably for another year...

Dabrafenib, trametinib, vemurafenib, and a lot of these drugs are...oral, you take them once or twice a day.  Whereas, virtually all of the immunologic agents that are in development are given intravenously.  Ipilimumab, for example is given every 3 weeks and to be honest, ...we haven't settled on the optimal dose.  There is a big trial of the standard approved dose of the 3mg/kg vs 10. Ten may be better...what implications [might this have] for the cost, because it is not a cheap drug?  If it turns out that the FDA will now approve 10 instead of 3 are they going to triple the price? 

I should add...that the excitement at ASCO...was because there was a combination trial of one of the PD-1 drugs, nivolumab, with the CTLA-4 blocking drug, ipilimumab...where you see in a graph the bars up or down indicating shrinkage or growth, it looked like it was a targeted drug, it was so good.  Toxicity, on the other hand, was not so trivial...Now, not only are we thinking about how do you combine the targeted drug, now you think about how to combine the immunologic drugs, so that is 5 more years of work at least, to work that out, and that will be impressive.

...The key, what is the best sequence of a targeted drug and an immunologic drug?...and it is not just a (single) drug.  It is what combination of targeted drugs and what combination of immunologic drugs, what should be the proper sequence? ...  That is a major unanswered question...

Fendrick:  What can you say about a standard of care, or a lack thereof, in metastatic melanoma...?

Weber:  ...There are the NCCN guidelines...

Malin:  ...before this call, I checked how...NCCN was recommending use of the 2 new B-RAF inhibitors...FDA approved in May, and NCCN hasn't updated its guideline...there is a little bit of lag...

Weber:  I think practices will vastly vary at an academic center like mine where you have 25 melanoma trials.  At UCLA I'm sure it's the same. It is going to be a little different than if you are in Albuquerque, New Mexico, at a good private practice with 5 other oncologists.  It is going to be very, very different as to what you can offer the patient.

Malin:  This brings up the issue of access.  These therapies are very exciting and the benefits that some patients have are really tremendous.  It is exciting to see someone go into a complete remission following 4 treatments with ipilimumab and stay in remission...for a year...  But, the wholesale cost of just the $120,000... Most small, independent practices (are) concerned about...taking on the financial risk of a drug that is that expensive without knowing whether the patient's insurance is going to cover it, whether the patient can afford whatever their copay might be.  If they have a 10% copay, that is $12,000 right there, so the cost of these drugs, at least in combining them, is going to bring new questions regarding access for people...

People can have long remissions...and some...benefit from retreatments...Does it mean someone is going to need to repeat treatment every couple of years?  ....When someone gets treated in the outpatient setting, usually the cost is double or triple, so just for ipilimumab, we are looking at a cost to the patient's payer....of $240,000 - $360,000...

Weber:  I think this is something that is at the top of everybody's consciousness...just about every professional group is going to emphasize the idea of trying to have biomarkers to select the right patients.  You can't just treat 100 patients and benefit  8 of them.  It is not going to happen in the future, the FDA has made it very clear how important they think biomarkers are.  ...  I predict that you are not going to get the (Oncologic Drugs Advisory Committee) and the FDA to approve drugs or push forward unless there is clear significant value; a 5 week prolongation of survival is not going to cut it in the next 10-20 years, not when the drug costs $120,000 for the wholesale price....

I suspect if you graph the price of current drugs over the last 20 years, you would see at least a linear increase with a doubling every 5 years and eventually what is it going to be, $300, $400, $500 or $600,000 to treat someone?  That is not practical....I'm not an economist, but I find it hard to believe that for [drug companies] to stay in business they need to charge $200,000 a year for dabrafenib and trametinib.

Ribas:  ...In places like the county hospital, it is hard to find any patient who has been on ipilimumab because it has not been approved for administration even though it is an FDA-approved drug and there are randomized trials that demonstrated approval and survival.  Those randomized trials showed improvement that is based on a small percentage of patients, around 10-15%...  We don't have a marker and possibly we will not have a marker, because it is an agent that is activating the immune system very far away from the tumor, so there are several thousand genes that are involved... It is unrealistic to think that there is going to be one biomarker that says this works or doesn't work in patients... We have dedicated over 5 years of research...and we are back to where we were...we give it to everyone because we don't want to miss those patients that can go on to have decades worth of of metastatic melanoma. That is something I have trouble putting a price on, but the worst case is when we don't even have the chance to give it, and that is what is happening with the price of ipilimumab being so is not only the wholesale price, it is the total bill that I see, and I am outraged every time a patient comes and says, this is what your clinic charged my insurance to give 4 doses of ipi.

Weber:  We have...the occasional referral...a charity patient who has either Medicaid from another part of the state, like someone from Miami, and the University of Miami will not treat them....and Moffitt will eat the cost of some percentage [for] those patients, or BMS will make the drug essentially free... A lot of companies have these programs where if you can't get anybody to pay for it, they will give you the drug for eventually it happens, but it can be a huge hassle...

Ribas:  There are patients who don't get to our clinics.....when I talk to doctors [in county hospitals], they tell me that it is very seldom [they] are able to give ipi to a patient because of the cost.

Weber:  I can see that being an issue for the poorest patients....this was a huge [an] Advisory Board I recently attended at ASCO....the question was, what if the price were $300,000 or $400,000 to get treated with some regimen lasting a year, would that be realistic? 

Fendrick:  ...I want to ask one thing that comes up a lot...what [do you think] about the idea of a situation where patients would get better coverage...if they went to Centers of Excellence for specific types of cancers?  Do you think it would be a good idea or a bad idea for particularly rare cancers to follow a model that we've had in place for transplants for decades?

Weber:  ...I wouldn't have a problem with seeing more patients and bring more business to places that excel at what they do.  To be honest, if I had metastatic melanoma...I would probably go to the big center, no question...

Ribas:  I would agree.  Sometimes we see patients on a second opinion, coming from the community. The data the community doctor has are the same as we have, the drugs are the same, but the usage may be wrong because they are not thinking about melanoma every day.  My thinking is that regardless of the cost, if we treat, it is cheaper than if we don't treat.  I mean treat...a medical condition and the medical condition improves...

...With all of this discussion I wanted to bring up one thing...I know is going to change even further...the PD-1 and PDL-1 antibodies are going to change...the treatment of melanoma again within the next 2 years...   If we look at the data right now, [it] suggests that we will get a significant fraction of patients with metastatic melanoma to have durable responses with therapies that are basically non-toxic or [with] serious side effects that need [intervention] and will leave the patient in the hospital....There are 7 of those PD-1, PDL-1 antibodies in the clinic [under] development right now....  3 of them...positioned to have licensing potential in melanoma and maybe many other cancers.

Malin:  ...Clearly the cost of these new drugs is a just a few years...the cost will be half of the median family income.  So, clearly, it is not conceivable that costs can continue to go up...  The good news is we think that 30% of what we spend on health care is waste, so if we can figure out how to stop doing the things that don't help people, we can insure that we can continue to make sure to make new therapies that are highly innovative available to people, but figuring out where that waste is, and getting people to stop doing things that don't provide value is challenging...

...You look at the fact that there are 3 aromatase inhibitors that have gone generic, in 2 of them the price dropped to $20 per month [yet] one of them is still $300 per month, but most oncologists don't even realize there is a difference in price, that either the patient...or the employer is paying...a difference in cost for a very active therapy that is equally effective...

Fendrick:  ...on the issue of clinical nuance, [it] is critically important that differ in the value that they create and the current benefit designs that patients see.  They pay the same out of pocket for lifesaving drugs as they do for drugs that I wouldn't give my dog... [We need to make] those services on which the evidence is strong accessible to patients and profitable to providers, and hopefully turn the corner and no longer make it profitable or easily accessible to patients, for which the evidence is weak, or in some cases, where there is true evidence of harm.

Audio link to discussion between Weber, Ribas, and Malin

Money, money, money!  My current working theme, huh?  Makes me tired.   - c

Tuesday, November 12, 2013

Counting Stars

So many thoughts lately. People once trusted. Their betrayals.  Lies I've believed.  Working so hard to live.  Facing fears.  Facing pain.  What does one do when you cross all those bridges?  Do you dare...HOPE?  That four letter word?  How do you prove it was worth it?  To the world?  To yourself? But I know, if perversely.... Everything that kills me makes me feel alive!

Counting Stars - One Republic

Lately, I've been, I've been losing sleep,
Dreaming about the things that we could be.
But baby, I've been, I've been praying hard,
Said no more counting dollars
We'll be counting stars, yeah we'll be counting stars.

I see this life like a swinging vine 
Swing my heart across the line.
In my face is flashing signs
Seek it out and ye shall find.
Old, but I'm not that old.
Young, but I'm not that bold.
I don't think the world is sold
I'm just doing what we're told.
I feel something so right
Doing the wrong thing.
I feel something so wrong
Doing the right thing.
I could lie, could lie, could lie...
Everything that kills me makes me feel alive.

I feel the love and I feel it burn
Down this river, every turn.
Hope is a four-letter word.
Make that money, watch it burn.
Old, but I'm not that old.
Young, but I'm not that bold.
I don't think the world is sold
I'm just doing what we're told
I feel something so wrong
Doing the right thing.
I could lie, could lie, could lie...
Everything that drowns me makes me want to fly.

Take that money, watch it burn.
Sink in the river the lessons I learned.
Take that money, watch it burn.
Sink in the river the lessons I learned.

Everything that kills me....makes me feel alive.

Lately, I've been, I've been losing sleep
Dreaming about the things that we could be.
But baby, I've been, I've been praying hard
Said no more counting dollars
We'll be counting stars.

We'll be counting stars.

Everything that tried to drown me...makes me want to fly.
Thanks, One Republic (and Rosie for sharing).  You said it well.
For all of you, come with me. Let's fly.- c

Saturday, November 9, 2013

For the love of money....BMS, Roche, and Merck

Money, money, money, money....O'Jays

(Click the link above...and let it roll while you read below!!!)

Money, money, money, MONEY
Some people got to have it
Hey, hey, hey...some people really need it.
Hey, listen to me, y'all do thangs, do thangs, do thangs - bad thangs with it
Well, you wanna do thangs, do thangs, do thangs - good thangs with it - yeah

FierceBiotech:  MK-3475, Merck.  October 8, 2013. By John Carroll
Peak sales potential:  Maybe $500 million for melanoma with the blockbuster money coming if a whole lineup of cancers is added.    The scoop:  Merck needs this one badly... Under growing pressure from Wall Street, which has come to expect nothing but disappointment, delay and failure from Merck over the past few years, the pharma giant is circling its best research wagons around this PD-1 immunotherapy drug.....turning heads at ASCO last summer...barring a big blowup in the clinic, this program has the potential to prove that the company still knows how to do serious drug research effectively.  The stakes are incredibly high, with no room for failure or even temporary delays.

FierceBiotech:  Nivolumab, Bristol-Myers Squibb.  October 8, 2013. By John Carroll
Peak sales potential:  Analysts have pegged peak sales potential at around $6 billion for nivolumab and the breakthrough BMS drug Yervoy.  The scoop:  Two years ago at ASCO the deal makers were circulating the halls in search of new immunotherapy programs to bargain over.  This past summer, the first round of human data started coming in in a big way, and the incredible promise of these therapies to add significantly to survival times, after years of incremental steps, moved drugs like nivolumab directly to center stage in the big cancer meeting in Chicago.  Bristol-Meyers isn't wasting any time in exploring the full potential for this therapy.  It has 6 late stage studies under way for nivolumab, with fast track status in place for melanoma, lung cancer, and kidney cancer.  If the data continue to come in to support these early results, BMS will have a major new therapy to rely on.

FierceBiotech:  MPDL3280A/RG7446, Roche.  October 8, 2013. By John Carroll
Peak sales potential:  As a leader among the top three immunotherapy developers, Roche is widely seen as a top contender for a drug capable of earning $2.5 billion to more than $3 billion a year.  The scoop:  While Merck's MK-3475 and Bristol-Meyers Squibb's nivolumab operate on PD-1, Roche believes it can have the same impact on cancer by hitting the opposite end of the target: PD-L1 .  Roche has an immense amount of cachet in the cancer field.  Its acquisition of Genentech put it in charge of one of the most impressive development outfits in the world.  All leaders in the field are racing ahead, gathering human data in a lunge for early approvals.

All those poor little rich boys, running super rich companies, lurking in the halls of ASCO meetings....all to save the lives of dying, suffering patients.   Right?  I mean, that's what it's all about right?  Not Wall Street.  Not market share.  Not profit margins.  Patients.  Right?  Right?????

For the love of money, People will steal from their mother.
For the love of money, People will rob their own brother.
For the love of money, People can't even walk the streets,
Cause they never know who in the world they're gonna beat
for that mean, oh mean, mean green.

Almighty Dollar!  Cash Money!
For the love of money, Don't let it, don't let money rule ya.
Don't let it, don't let money fool ya. 

"Human data" for big pharma.  Hmmm....  So, that's what I am?  Interesting.  And to think how much I had to pay to be in THEIR make THEIR numbers look good.  Glad things are looking up for all of them.  Hang in there ratties.  Hang in there.  I always said, long tails come in handy.  - c


Wednesday, November 6, 2013

Ipi, BRAF/MEK, Anti-PD1 [and NO MORE DACARBAZIN???!] - per chat with Antoni Ribas

A conversation in the wake of data presented at the European Cancer Congress 2013....

Ipilimumab Goes the Distance in Melanoma
Antoni Ribas, MD and Caroline Robert MD.  October 8, 2013 [excerpts]

Ribas (David Geffen School of Medicine at the University of California Los Angeles):  We have BRAF inhibitors, the BRAF plus MEK combinations, ipilimumab, PD1, and PD-L1 antibodies. We have heard important updates... Let's start with the long-term updates on ipilimumab (ipi).

Robert (Dpt of Dermatology at the Institut Gustave Roussy in France):  We are happy to see that plateau with...ipi.  We would like to have more patients responding, but we are happy to see that when patients survive at 3 years, the odds are that they are still going to survive at 5 years.

Ribas:  [We] have talked many times about this hallmark of immunotherapy - that when you have a good immune response to the cancer, that can be extremely durable.....we are seeing that play out with ipi, which is great information.

How is [the combination] of BRAF and MEK inhibitors improving on what we have with BRAF inhibitors alone?

Robert:  It is the ideal combination...together, [these 2] drugs, have better efficacy with a longer duration of response, and you have fewer adverse events.

Ribas:  ...the data from dabrafenib and trametinib (BRAF and MEK inhibitors) published in the New England Journal of  Medicine, suggesting a higher response rate, a more durable response with fewer skin side effects from blocking a paradoxical MAPK pathway activation.  [In another study], a dose escalating phase 1 trial using vemurafenib, a BRAF inhibitor, with cobimetinib, ..another MEK inhibitor.  By putting them together...the response rate was extremely high.  They reported a 95% objective response rate.  It is close to a near guarantee of having a response at these levels, and we haven't reached the median progression-free survival, telling us that the curve is staying up quite a bit.

As we get more responses, are they lasting longer?  The BRAF-plus-MEK combination is telling us this.

Robert:  Unfortunately, what we hear is that when patients have failed a BRAF inhibitor previously, then not a lot of them respond.  Only about 15% of patients responded.

Ribas:  This study is telling us something...biologically important....we can get a secondary response by adding a MEK inhibitor to patients who are progressing on a BRAF inhibitor.  Whenever there are mechanisms that are dominant in activating MEK...all of theses patients respond.  The problem is that it is not a durable response.  And when we add the MEK inhibitor, we find another mechanism of resistance. So, melanoma is still trying to fool us, but we are also making progress on other fronts, by taking away another checkpoint:  PD-1 and PD-L1.

RobertWe are amazed at the results that we see with PD-1 blockade....a lot of patients responding: 30-40%. And though we have less follow-up than we have with the drugs that are on the market, we have the feeling that we are seeing long-term responses, and the side effects are not bad.  Now we think that it can be combined with an anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4)  {like ipi} agent for an even higher level of response.

Ribas:  ...follow-up data on the combination of ipi (an anti-CTLA-4 blocking antibody) and Nivolumab (a PD-1 antibody)...[shows] a very high rate of objective responses, more than 50% in the dosing regimen that is taken forward, with most responses continuing on.

RobertThis is also why we might now have to change our endpoint....when we know that we have drugs that are so effective, to wait until overall survival is confirmed at the end of a phase 3 study.  What do you think about using progression-free survival as an endpoint for our patients?

RibasFlaherty (from Mass General) presented... a study in which they looked from patients who were in randomized trials that had dacarbazine as the control arm.  We are not even using this word anymore in conversations about melanoma because so many agents have improved overall survival....and taking all the studies...comparing ipi and dacarbazine vs dacarbazine, ...vemurafenib vs dacarbazine, dabrafenib vs dacarbazine, and trametinib vs dacarbazine - all of these studies have shown that another treatment was better than our old standard.  For you and me it is difficult to sit in front of a patient and talk about the control group to which (for the purpose of the phase 3 study) we cannot give a highly active agent that is already out there.  Knowing that progression-free survival may be a hard endpoint that correlates with overall survival would be a great thing.

Amen!  Stop using crap as a control arm.  Patients deserve better.  As a last ditch effort, when all else has been tried....sure....if the patient wants to throw some dacarbazine at all means.  But, stop wasting rattie time, energy, dollars and lives in testing new and better drugs against old meds we know they beat already.  To continue to do so does not produce effective trials....only pseudo science.  And benefits whom?  Drug companies?  It certainly doesn't help anyone else!

Hang in there ratties!!! - c

Sunday, November 3, 2013

Melanoma patients...alive and kicking 10 years after ipi!

Only in melanoma (and a few other horrifying diseases) is ten years post treatment an amazing wonder and something to cheer about!  Oh, well.  We'll take it!

Some Melanoma Patients Living for up to 10 years After Ipilimumab
By: Zosia Chustecka. September 28, 2013 [excerpts]

The dramatic impact that the immunomodulator ipilimumab [ipi] (Yervoy, BMS) made on the treatment of advanced melanoma is shown in new long term data reported at the European Cancer Congress 2013.

Dr. Hodi presented long-term data from a pooled analysis of 4846 patients, which showed a plateau in the overall survival - with 21-22% of patients alive at 3 years, 17% still alive after 7 years, and no deaths after that.  "The longest follow-up in the database is 9.9 years," he said.

"This is a huge paradigm shift in the treatment of melanoma from where we were just a few years ago," he said.  "What it means for us as clinicians is that we can start talking to our patients about the possibility of turning melanoma into a chronic disease, which we couldn't even imagine a few years ago."

Ipi, approved in 2011, in Europe and the US, has a novel mechanism of action, interfering with the immune system instead of acting directly on the cancer. It targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a protein found on the surface of T cells that acts like a brake; the drug removes the brake, allowing the T cell to go into attack mode and kill cancer cells.  This product is typically given as a course of 4 injections during a period of 3 months, and some patients receive retreatment and/or maintenance therapy.

For some patients it seems that this short treatment is enough to reset the immune system and reach a new which "tumor cells are still present, but are being kept in check by the immune system," Dr. Hodi explained.

He noted that response rate to ipi is low, only about 10-15%, but in some patients, a few doses of this drug result in long-term survival: "more than 3-10 years' survival in 17-25% of patients."  He predicted that these survival results will be improved further with the anti-PD1/PDL1 monoclonal antibodies that are in development.

The long term data come from a retrospective pooled analysis of patient data collected from clinical trials as well as expanded access programs in which patients were treated before [ipi] was approved.  [It included previously treated and untreated patients, getting 3 or 10mg/kg doses, given every 3 weeks for 4 doses, and with or without, retreatment or maintenance therapy.]

None of these variables appeared to have had an impact on survival.  "The plateau, which started at 3 years and continued through to 10 years, was observed regardless of dose (3 or 10mg/kg), whether the patients had received previous treatment or not, and whether or not they had been kept on a maintenance dose of the drug," Dr. Hodi said....he emphasized that this was not a randomized comparison, so direct conclusions cannot be drawn.  "However, these results are consistent with our findings from randomized trials and confirm the durability of the plateau in overall survival, previously shown to extend to 5 years but now shown to extend up to 10 years."

Just think, ipi was not even on the market when I started this Stage IV journey.  May even greater improvements that facilitate a lasting response in a much larger percentage of patients be available SOON!!!! - c

Friday, November 1, 2013

Melanoma Avengers....Cool Running!!

Check out the links:

Running Rosie

13 miles later...

Fast Freddie at the Finish!!!

My most amazing avengers, running buddies, best pals, and the most wonderful kids...EVER!!!!
Much love - mommy