Battle = Biomarker-integrated Approaches of Targeted Therapy for Lung cancer Elimination. Approaches like this is one of the major reasons for driving us towards MDACC. It's a rather innovative way at conducting clinical trials. The standard way of looking at new therapies is take a thousand patients with lung cancer and say half get treatment A and half get treatment B. The problem is that not all lung cancer patients are equal and at the end of the trial, the primary endpoint would often be missed (translation - expensive failure) but in further analyses it may be found that one small percentage may have benefited. Then one would have to conduct another trial and look at those patients and so on. At the end of the day, it has not lead to much progress in lung cancer. This approach hopes to change that.
They biopsied non-small cell lung cancer patients (NSCLC which is what my brother has) who had already undergone chemo and assessed the tumor for 11 different mutations or particular markers. The first round of initial patients were randomized to one of four different experimental therapies that would inhibit molecular pathways thought to be important in cancer biology. The goal was to find out which therapies worked in which markers, or just as importantly, what therapies would not work in certain patients. After the first round they would then engage a technique called adaptive randomization. It's a bit like artificial selection in medicine. If patient with markers A, B, and C responded to Therapy 1, then the next patient who came along with markers A, B and C would be nudged towards that same therapy. Likewise, if the same patient responded horribly to Therapy 2, the next patient would be nudged away from Therapy 2. It's an iterative process that moves away from a shotgun approach and instead allows for a system to adapt and improve through a darwinian process thereby minimizing costs and failures.
So how did it work? First, it showed that a targeted trial using adaptive randomization could work (also see I-SPY for breast cancer) which was not a foregone conclusion. I suspect that this will slowly but surely begin to change the way cancer trials are conducted. Second, since these were end stage patients who had already undergone the usual therapies, the primary endpoint was 8 week control of the disease (that means that the tumor had maintained size or shrunk after 8 weeks by imaging). Historically, that would mean about 30% of the patients would meet those criteria after 8 weeks. With this approach, it reached 46% which is not at all trivial in very sick patients. And since they collected good biopsies, they and other researchers can go back and further probe the biopsies with new information and newly discovered mutations. Now the plan is to take the information learned and go into a BATTLE 2 and BATTLE 3. If you want more nuts and bolts about the mutations and therapies, you can click here (listening to one patient who was 37 and a triathlete was very poignant). If you want to listen to a podcast with the clinicians and two of the patients enrolled, you can click here or you can find it iTunes here (it should be podcast #17 with BATTLE in the title).
I walked away with two distinct impressions. First, when asked about some of the pragmatic results that can be immediately applied to oncologists, the clinicians stressed the importance of high quality biopsies. As I look back on my brother's experience, I can attest firsthand to the inadequacy of biopsy harvesting at other institutions (they screwed up the first one which still makes me furious to this day). The second was something I came across on the web. Since I haven't yet had a chance to discuss the results with the doc, I perused around a lot on the web reading other oncologist's opinions and thoughts about it. I came across this forum where an oncologist gave this assessment of the trial which I found amusing:
I think they are encouraging and provocative and show the feasibility of a concept for which feasibility was actually an open question....Part of what he's talking about is that MDACC trials often have highly motivated patients so they can produce results that others may not be able to. The other is that the comprehensive nature of care there is so wide and cutting edge that it dwarfs many other institutions. And for both of those reasons, it feeds me hope because my brother is a highly motivated patient and the quality of care he has received there has been top notch.