Friday, March 20, 2009

Ch14.18 Increases Survival!

Without a doubt in my mind, this is the most significant discovery for children with neuroblastoma - certainly since Sydney was diagnosed, surely in the last decade, and quite likely in the history of the disease. Yesterday afternoon the COG publicly released a statement regarding the early study results of ANBL0032 (A Phase III Randomized Study of Chimeric Antibody 14.18 (Ch14.18) in High Risk Neuroblastoma Following Myeloablative Therapy and Autologous Stem Cell Rescue.)

In it they state that the immunotherapy (experimental) arm of the study – a combination of ch14.18 antibody, cytokines (IL2 and GMCSF) and Accutane more effectively reduces the risk that neuroblastoma will grow back than treatment with Accutane alone. Furthermore they have determined that the immunotherapy, as specifically delivered on COG ANBL0032, increases the chance of survival after completion of therapy including stem cell transplantation when compared to treatment with cisRA alone. According to the statement they now expect that this immunotherapy may eventually become a standard part of high-risk neuroblastoma treatment after stem cell transplant.

For more information, the complete statement can be found here:

You may recall not to long ago that I was still beating my drum in my blog about antibodies. For years I have stated that I have seen kids with neuroblastoma. I have seen kids with neuroblastoma be treated with antibodies. And, that I have seen their disease disappear. My argument has always been about response. I have seen responses. This finding is much different. This finding is that they have not only seen responses but they have seen a significant increase in survival. Not only did they see an increase in survival but it is clearly dramatic enough that they were able to stop the trial early (3+ years early). This is proof for parents everywhere that ch14.18, when given after transplant with GM-CSF and IL-2, significantly increase survival.

In all do honesty, this finding does come as a little shock to me (as well as many others). You may remember that I commented here not to long ago that I did not see how there could be a dramatic change given the results of A3793 which included many of the patients on this study. No one could see the math working. We could envision the possibility of a long term survival advantage but nothing, nothing like this. These results blew the roof off the study and I, for one, could not be more ecstatic. After all, Sydney participated in this study and was lucky enough to be randomized to receive the ch14.18 antibody.

Since finding out the news my mind has been racing with questions and thoughts on how this result will change the face of neuroblastoma. One of the most urgent concerns I know for most parents will be "How do we get the antibody?" At this point, that is clearly a difficult questions to answer. While I presume they will amend the study to remove the randomization so that all kids receive the ch14.18 antibody that is but one step in the right direction. You see, currently the trial is on hold by the FDA while they review some recent toxicities. Right this moment, no one can get the antibody on this trial. Secondly, even when the antibody becomes available where will you be able to get it? Only about half of the COG institutions offer the therapy. Each of those will still have to get the ammended protocol changes through their institutional review boards (IRBs). Institutions that did not have the antibody will still have to not only do that but also go through some fairly extensive staff training. Third, it isn't like an unending supply of this mouse stuff is sitting in a big vat somewhere. There was a limited supply for this study and only for the number of kids that were going to be randomized. They will have to make more - although I am sure they are already working on that. Wow, I could sit and write questions all day. Unfortunately, I guess we will all have to just hold on to our britches for a bit longer while they work diligently to sort this all out. This has far reaching impact.

On another note, while I feel tremendous happiness that we were randomized to receive this antibody I also feel deeply for so many friends that participated on this study but were randomized not to receive this antibody. I know it is a bitter sweet day for them leaving even more questions floating through their minds. I thank them all for their participation and I know that there will be 1000s of kids and families who follow that will feel that way as well. Randomized phase III trials can be both a blessing and a curse. They are a blessing when they can provide a clear answer as to which treatment may be best, as they did in this case. Now we know for sure that more kids will live because of this study. However, they are a curse because ultimately half of the children were randomized not to get the treatment that was later found to be important. In that sense, it is tremendously unfair. And, it is for those families that I am tremendously appreciative.

Purpose can be bitter sweet but, for all those that follow, today is a better day in the world of neuroblastoma than yesterday.

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