Not too sure what to believe anymore

Linda, do you have a handy source for the 10-15% total responders?   (And for the length of the response?)

I also wonder what the long term total responders % and length of time) will be.  (Hard to tell  untill more time passes.  The trial that I heard the highest response rate, seemed to have had some restriction as to who they tested on.  We're getting closer, but what does what on just who is still too far from being known.  (I want to know NOW!)

Linda, do you have a handy source for the 10-15% total responders?   (And for the length of the response?)

I also wonder what the long term total responders % and length of time) will be.  (Hard to tell  untill more time passes.  The trial that I heard the highest response rate, seemed to have had some restriction as to who they tested on.  We're getting closer, but what does what on just who is still too far from being known.  (I want to know NOW!)

Jerry,

I am going to quote from something I printed last night. The article was titled "Beyond Ipilimuab: New Approaches Target the Immunological Synapse" by Ken Garber.  

jnci.oxfordjournals.org  Vol 103, issue 14, July 20, 2011.  I am of course taking this little paragraph out of an almost 4 pg. article.  "But ipilimuab's objective response rate is only 10%-15%, and the drug sometimes causes severe immune-related side effects."  They use the same stat later in the article when comparing it to PD-1 drug. 

If you want the entire article I'll try and see if I can link. 

Linda
 

Jerry,

I am going to quote from something I printed last night. The article was titled "Beyond Ipilimuab: New Approaches Target the Immunological Synapse" by Ken Garber.  

jnci.oxfordjournals.org  Vol 103, issue 14, July 20, 2011.  I am of course taking this little paragraph out of an almost 4 pg. article.  "But ipilimuab's objective response rate is only 10%-15%, and the drug sometimes causes severe immune-related side effects."  They use the same stat later in the article when comparing it to PD-1 drug. 

If you want the entire article I'll try and see if I can link. 

Linda
 

So true.  "Fun to be on the forefront?" 
Should I comment on what a friend of mine said about the first two letters of the word "FUn"?

So true.  "Fun to be on the forefront?" 
Should I comment on what a friend of mine said about the first two letters of the word "FUn"?

That was meant as a funny, not anything personal.  As Charlie says make the best decision you can as to what feels the best to you on the science you follow.  Don't second guess, we don't have time for that.  Do look ahead and make plans for the what if's. 

That was meant as a funny, not anything personal.  As Charlie says make the best decision you can as to what feels the best to you on the science you follow.  Don't second guess, we don't have time for that.  Do look ahead and make plans for the what if's. 

FUn…indeed!!! (Who'd not want to be a part of all the excitement?!?!??) 😛

Jerry, your comment made me laugh, and made me think of a Monty Python skit:

My response is not meant in an inflammatory way, in fact I'm laughing as I type some of this, but I really want some of this to be heard re: BRAFV600E.

Monty Python skit with "You lucky, lucky %@$!@^*!" is in the forefront of my mind while I type this, in order to address a common misconception. (And Lisa, it's not aimed directly at you- I've heard it several times)

Considering it means a "greatly elevated B-Raf kinase activity and constitutive activation of MAPK/ERK downstream…” (For example B-RafV600E exhibits elevated kinase activity that has been estimated to be 50–100-fold more potent than wild-type B-Raf", I’m not altogether sure that “lucky” is a word I’d use. In fact, it’s not a word I associate with melanoma at all)

Maybe (just maybe) WITHOUT that mutation, I’d not have developed 50+ brain mets, and a mass on my adrenal, numerous sub-q’s throughout my body and 3 liver mets, in the space of 2 months which required me to start on a BRAF-i in the first place? (Which, might I add, I am coming off in 2 weeks due to progression, after a mere 3 months effectiveness? Did I forsee that? No- I’d hoped for 6-9 months. But I’m not looking back or questioning my choice of drug. For others it works longer, just not for me. C'est la vie.)

After a while, most people work out that it’s just hopping from stepping stone to stepping stone, and hoping researchers stay a few steps ahead of us. Never look back! You do what you do because you use the best information you have available at the time. (Even with limited choices, we still choose whether to gamble or not to do anything)

I’ve chosen Yervoy as my next gamble. (It was my first choice years ago, but I was ineligible for it, and every other trial that interested me, for various reasons) So several stepping stones later, I end up where I wanted to be originally. A few months here, and a few months there have added up to over 3 years (a veritable lifetime compared to some others) with my daughter… and still Yervoy has no guarantee of success. But I’ll finally be able to have a shot at it. Maybe it’ll work. Maybe it won’t. But it’s the best decision I can make for the moment, and I’m going with it- and I won’t look back. A seer, I’m not. A risk:benefit analyser I am.

Nic 😀

FUn…indeed!!! (Who'd not want to be a part of all the excitement?!?!??) 😛

Jerry, your comment made me laugh, and made me think of a Monty Python skit:

My response is not meant in an inflammatory way, in fact I'm laughing as I type some of this, but I really want some of this to be heard re: BRAFV600E.

Monty Python skit with "You lucky, lucky %@$!@^*!" is in the forefront of my mind while I type this, in order to address a common misconception. (And Lisa, it's not aimed directly at you- I've heard it several times)

Considering it means a "greatly elevated B-Raf kinase activity and constitutive activation of MAPK/ERK downstream…” (For example B-RafV600E exhibits elevated kinase activity that has been estimated to be 50–100-fold more potent than wild-type B-Raf", I’m not altogether sure that “lucky” is a word I’d use. In fact, it’s not a word I associate with melanoma at all)

Maybe (just maybe) WITHOUT that mutation, I’d not have developed 50+ brain mets, and a mass on my adrenal, numerous sub-q’s throughout my body and 3 liver mets, in the space of 2 months which required me to start on a BRAF-i in the first place? (Which, might I add, I am coming off in 2 weeks due to progression, after a mere 3 months effectiveness? Did I forsee that? No- I’d hoped for 6-9 months. But I’m not looking back or questioning my choice of drug. For others it works longer, just not for me. C'est la vie.)

After a while, most people work out that it’s just hopping from stepping stone to stepping stone, and hoping researchers stay a few steps ahead of us. Never look back! You do what you do because you use the best information you have available at the time. (Even with limited choices, we still choose whether to gamble or not to do anything)

I’ve chosen Yervoy as my next gamble. (It was my first choice years ago, but I was ineligible for it, and every other trial that interested me, for various reasons) So several stepping stones later, I end up where I wanted to be originally. A few months here, and a few months there have added up to over 3 years (a veritable lifetime compared to some others) with my daughter… and still Yervoy has no guarantee of success. But I’ll finally be able to have a shot at it. Maybe it’ll work. Maybe it won’t. But it’s the best decision I can make for the moment, and I’m going with it- and I won’t look back. A seer, I’m not. A risk:benefit analyser I am.

Nic 😀

Found the article extract (cannot get the whole article) and also found a definition of terms :

http://cancerguide.org/endpoints.html

Objective Response (OR): Objective response means either a partial or complete response (In the literature you'll frequently see "CR+PR" which means the same thing). When you see an objective response rate be sure to look at how many are complete responses and how many are partial since benefits from complete response tend to be greater. Often news reports and especially press releases by self-interested companies blur this and don't reveal that the CR rate is low or non-existent. Track down the original source and find out!

**********************************************8

This article for one study seems to give an even lower response rate than il-2, not a higher one. 

Found the article extract (cannot get the whole article) and also found a definition of terms :

http://cancerguide.org/endpoints.html

Objective Response (OR): Objective response means either a partial or complete response (In the literature you'll frequently see "CR+PR" which means the same thing). When you see an objective response rate be sure to look at how many are complete responses and how many are partial since benefits from complete response tend to be greater. Often news reports and especially press releases by self-interested companies blur this and don't reveal that the CR rate is low or non-existent. Track down the original source and find out!

**********************************************8

This article for one study seems to give an even lower response rate than il-2, not a higher one. 

Linda, Would like a copy of the full article if possible.  Thanks, Jerry

Linda, Would like a copy of the full article if possible.  Thanks, Jerry

I'll try this link. If it doesn't work I'll scan it in and send it to your e-mail.

 http://safefromthesun.org/pictures/1079.full.pdf
 

Linda

I'll try this link. If it doesn't work I'll scan it in and send it to your e-mail.

 http://safefromthesun.org/pictures/1079.full.pdf
 

Linda

Got it  .  reading it now.

Thanks

Got it  .  reading it now.

Thanks

The PD-1 line is one that seems to be a possibility for helping enhance the c-kit attack.  I've been watching that developemnt to. 

Finding Winning Combinations
Although the FDA approved ipilimumab as single-drug therapy for melanoma, “the name of the game now is going to be combination therapies,” said Suzanne Topalian, M.D. , of
Johns Hopkins. A trial of ipilimumab with an experimental anti – PD-1 antibody ( see story) is just the first of many.
The potential combinations are dizzying. Besides combining two immune checkpoint
inhibitors, each could be used together with a costimulation activator. Other options
include cancer vaccines, adoptive cellular immunotherapies, or kinase inhibitors. Even chemotherapy makes sense as a way to unmask tumor antigens to a boosted immune system. “There aren ’ t enough people or days or patients to test all the very interesting things that can be done,” said oncologist Mario Sznol, M.D., of Yale University at a recent grand rounds talk at Yale. “One of the things that we need to do is fi gure out what are the critical nonredundant pathways and target those, so we don ’ t waste a lot of time inhibiting two targets that are in the same pathway.”
Predicting which patients are likely to respond to immunotherapy is another crucial
task that has barely begun. For example, no one knows why some patients respond dramatically to ipilimumab or anti – PD-1 antibodies, whereas most patients have no objective tumor responses at all. Efforts to identify predictive markers are under way, but the task is daunting. In a phone interview, Sznol said that an immunotherapy biomarker “probably depends on things that the tumor does, things that the infi ltrating cells do, things about your prior immune system, maybe even some genetic component . . . [and on] where you are in the stage of the disease. It ’ s very complex. So I would imagine that we’ll never find one single thing that ’ s going to be 100% predictive.”

The PD-1 line is one that seems to be a possibility for helping enhance the c-kit attack.  I've been watching that developemnt to. 

Finding Winning Combinations
Although the FDA approved ipilimumab as single-drug therapy for melanoma, “the name of the game now is going to be combination therapies,” said Suzanne Topalian, M.D. , of
Johns Hopkins. A trial of ipilimumab with an experimental anti – PD-1 antibody ( see story) is just the first of many.
The potential combinations are dizzying. Besides combining two immune checkpoint
inhibitors, each could be used together with a costimulation activator. Other options
include cancer vaccines, adoptive cellular immunotherapies, or kinase inhibitors. Even chemotherapy makes sense as a way to unmask tumor antigens to a boosted immune system. “There aren ’ t enough people or days or patients to test all the very interesting things that can be done,” said oncologist Mario Sznol, M.D., of Yale University at a recent grand rounds talk at Yale. “One of the things that we need to do is fi gure out what are the critical nonredundant pathways and target those, so we don ’ t waste a lot of time inhibiting two targets that are in the same pathway.”
Predicting which patients are likely to respond to immunotherapy is another crucial
task that has barely begun. For example, no one knows why some patients respond dramatically to ipilimumab or anti – PD-1 antibodies, whereas most patients have no objective tumor responses at all. Efforts to identify predictive markers are under way, but the task is daunting. In a phone interview, Sznol said that an immunotherapy biomarker “probably depends on things that the tumor does, things that the infi ltrating cells do, things about your prior immune system, maybe even some genetic component . . . [and on] where you are in the stage of the disease. It ’ s very complex. So I would imagine that we’ll never find one single thing that ’ s going to be 100% predictive.”