Posted by Jeff Berk, BOLT International;
I’m sitting in the British Airways lounge at Sky Harbor airport. My flight’s delayed by 30 minutes because some inbred British guy wanted to make an honest woman out of some chick I never heard of. They’re serving “wedding punch”. I turned them down, and opted for the martini instead. I’m headed to Paris, another place besides Phoenix where nobody really cares about the British monarchy. So I’m not posting a cactus flower today. Instead here’s public response to the guy from New Jersey who emailed me and asked what was so cool about Arizona. Well, dude, you have some interstate in your backyard. Here’s mine.
Emails are running 50:50 from FDA defenders and panobinostat defenders. Interestingly, those who identified themselves as having a personal relationship with Hodgkin’s are ALL in favor of panobinostat approval. It’s like the bacon and eggs thing. The chickens at FDA’s are “involved” but patients (sorry guys, you’re the pigs in this analogy) are “committed”.
So tonight I want to share one of BOLT’s Lung Cancer Thought Leader’s perspectives on the BATTLE trial (non-small cell lung cancer), and what comes next in terms of getting patients on targeted therapy. We’ll be talking a lot more about this in our upcoming panel, which will publish in May 2011, but for now, a taste:
So punch line how do you take BATTLE and use that as a trial design or can you?
You may even be able to do one better than that. You may even be able to biopsy the tumor, put the patient through whatever other workup they might need which usually is not nothing. Usually they need a scan or they need an evaluation by a neurologist. They see the endocrinologist because their sugars are off the wall. Lung cancer has many comorbidities. You may be able to flip those results around in two weeks within a given institution or with closely allied companies that are going to do this at an extremely high quality and get a feedback on the patient’s mutation profile for up to say 200 cancer genes and 1000 mutations. And two or three years from now that is going to have overlaid copy number changes, epigenetics, gene expression from one or two core biopsies from a given site of disease. And then so that then behooves the center to work with industrial colleagues to have a broad swath of trials open as patients fall into those bins for treatment strategies. You may be able to get away from this adaptive control mechanism starting patient on X and then switching them after you get something back. The critical thing is that the tissue is that we are learning to get more tissue but we are also learning to do more with less including less cost. You read about all the stuff with dropping old genome sequencing. And we are not talking about that here, we are talking about something short of that, but truly an exciting time. I think it will make for a much better marriage between Pharma companies and academic medical centers who really believe this is the way to move forward.
Let me see if I am picturing this. So your center is going to contract with company X and they have got themselves an EML4 ALK and company Y has themselves a BRAF inhibitor and company Z has let’s say an FGF inhibitor. you have all these guys and you say to them we are going to screen all-comers, we are going to biopsy these tumors and if it is this we are putting your drug on, if it is that we are putting those guys drug on. Do I basically see that correctly?
Yes. And the thing to understand though that makes it really neat is that this testing will be done – you know we used to have a lung panel and a colon panel and a melanoma panel – we are thinking of developing an institution-wide panel that would be something like 200 gene 1000 mutations. So that every patient who comes to Memorial in essence with most of the common solid tumors at least would have that testing done. Then it is incumbent on what companies may do. Novartis may say we are going to open ten trials at once in a boutique setting at Memorial and a couple of other centers that are doing this and we will be able to fill those bins pretty quickly because they prospectively test everyone.
Right. One of the slides put up at AACR listed the following for non-small cell mutations, so it was EGFR 14 percent; KRAS mutant 20 percent; EML4 ALK 9 percent; BRAF 3 percent; PI3kinase 3 percent; HER2 2 percent. You add all that up and you are getting to 47 percent of tumors having at least one known driver to them. Contrast this to so it was at ASCO 2002 or something like that where the first EGFR trials were shown, and so you had very small percentage of patients where you knew how to target them. Is current therapy actually driving this quickly towards targeted therapy or are most patients still actually starting on just some platinum-based or taxane/platinum-base?
I think it has got a lot of legs. I think clearly you are hearing people who five years ago they would start the patient on chemotherapy and then get Tarceva second line or third line. Now you go to meetings and hear folks, and this is not only in the US but in other countries, and they are willing to get the tissue up front and steer the patient accordingly. EGFR as I say when I give a talk it is the beginning not the end. It is the watershed event that changes how we think about things. And another step to layer onto that is when you get this broader panel of mutations you may identify co-events that either explain why patients didn’t respond to erlotinib even though they had a mutation or they responded only briefly and therefore allow you to look at a combination study. So suppose the patient has EGFR mutation and a PI3 kinase mutation, or EGFR mutation and p53 with mutation and you thought you had something that addressed that. So the broader panel will allow combinations. And anytime you get to combinations and in turn is rational combinations, moving out progression free survival and overall survival and it is that much longer the individual is on the backbone drug and also a niche for the second drug being added to it, say the one targeting the accompanying mutation or the modifier mutation.