It's a great talk by Prof Thomas Tursz from EU. I agree that the status quo in BC clinical trial is not acceptable. Each semi-successful drug takes 15 years from bench to approval, 100s million dollars, not to mention the 9/10 failed drugs. Combination drugs may well help, (Herceptin, Everolimus, Pertuzumab all succeed in combination treatment) but there is a big problem with mathematics.
Usually a good treatment (not a specutacularly good 70-100% response treatment, maybe a 30-50% response treatment) takes 500 patients in a randomized blinded controlled trial to get statistically significant proof that it actually is good, not just a statistical fluke, a placebo. I explained this in another thread: A clinical trial on 23 patients is like 23 coin tosses. After 23 coin tosses, say I get 15 heads vs 8 tails. I could say that this coin is weighted heads/tails ratio almost 2, that's very different from 1. But I am not very confident of this conclusion because the sample size is too small. Now if I toss 500 times, and still gets heads/tail ratio of 2, then I become very confident of this ratio.
That's why randomized double blinded clinical trial with 500+ patients is still the gold standard in clinical trial. That's expensive and requires lengthy recruiting. When you consider that different subtypes of BC (TNBC, claudin-low, normal-like, basal) may have only 2%-10% patient population, you realize how tough it would be to find 500 patients with this small subtype to test a drug specifically targeting this type. Add to that cancers evolve to become drug resistant, it become even tougher.
Now, let's move on to the even more difficult tasks of testing combination treatment. Suppose we have 3 drugs (A,B,C) that has cleared phase II trial with good results, each requires 500 patients to go through phase III trial for approval, that's 1500 patients required total. Now if we want to explore combination treatment, then there are at least 4 combos, AB, AC, BC, ABC. That would require 7*500=3500 patients for a full test.
Suppose we have 4 drugs (A, B, C, D), there will be 15 combos+singles to fully test, requiring 15*500=7500 patients. Suppose we have 5 drugs, we will need 31*500 patients. So on and on.
It's exponential, doubling with every new promising drug to test and we do not have this many patients. But "In clinical trials, 97% of patients in Europe are not in a trial", I think numbers are similar in US. That is a HUGE problem.
Traditional clinical trials especially on early stagers require long time commitment (like 5 years) from patients. So traditionally late stagers are the main force of clinical trials. Late stagers are fewer in numbers (50000/year), the ones with the right subtype of BC rarer (say 5000/year for TNBC, which has more subtypes), the ones with good performance statuses are fewer still (say 2000/year), the ones with good performance statuses living near a research facility are rarer yet (say 1000/year), the ones with good performance status who are willing to serve in clinical trials are still fewer(I don't know how many, but certainly less than 50% from my observation), and so it's hard to recruit enough of them to test new drugs, much less combinations. End result is: traditional clinical trial process takes 15 years and 1 billion dollars for any good drug to make through.
This is why I'm so excited by ispy-2.org. Newly dxed early stagers needs to commit only months to either control or experimental arm. Basically a couple of dose to see if it (standard chemo or standard+new drugs) works, if not, they change chemo or go ahead to surgery. The new drugs are generally the most promising drug that has already been tested for safety. 200k/year newly dxed patients with good performance status could potentially be recruited which means quick recruitment. A new drug if demonstrating efficacy, could go from bench to approval in as little as 5 years. Even FDA is excited.
If Henry Ford is on Titanic, he would not say: let's do a handmade lifeboat for everyone. He'd make an assembly line that churns out lifeboats. Ispy2 is the kind of assembly line for new cancer drugs that he'd be proud of.
ispy-2 has potential to increase patient participation dramatically by reducing patient commitment. That said it only could test certain type of drugs. In general, we need much greater patient participation across the board, and we need a different clinical trial model with different end-point (phase I, II, III may need to be changed), we need to invest in better animal model/preclinical model, better blood/imaging tests for progression, different end-point. We will get the MBC cure, but the PROCESS for developing cure urgently needs to be improved.
