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May 22, 2005
That Has to Be Good, Right?
Posted by Derek
Here's a nice article over at Forbes which highlights a tough question: what's the best indicator of efficacy for a new cancer drug? One of the easiest things to measure is tumor shrinkage, and you'd think that would be a good sign. Common sense can only take you so far, though:
"But now doctors are finding that tumor shrinkage, on its own, isn't necessarily a good reason to use a drug, because it's entirely possible to shrink a tumor without helping the patient. More important measures of efficacy are how long it takes for the cancer to start worsening and how long patients live. If a drug increases survival time, its efficacy clearly outweighs any side effects."
Survival, of course, takes a lot longer to measure, and time is nowhere more equivalent to money than in a clinical trial. If we're going to start moving away from the classic response rate - number of patients with 30% or more shrinkage - then we're going to be spending a lot more to evaluate our drugs. It's true that the article linked above quotes someone who doesn't buy this logic, but he's talking about using some genetic marker as a surrogate. This is a very nice idea, but we're back to the same problem: it also takes years to prove that these things are linked to survival, and that'll always be the real standard. Who cares what your cancer is up to if it kills you on the same schedule?
No, using survival as the endpoint will almost always cost more. But I think it'll be worth it. I've never understood the benefit to desperate patients of giving them something that's just going to make them spend their last months being jerked around.
Comments (6)
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College chemistry, 1983
The 2002 Model
After 10 years of blogging. . .
1. David Govett on May 23, 2005 1:10 AM writes...
It could be argued that, unless every last cancer cell is eradicated by a treatment, it would be better not to treat, since only the most resistant and aggressive cells would be left, thereby ensuring an even faster death.
Permalink to Comment2. John Johnson on May 23, 2005 8:20 AM writes...
Except I don't think cancer works in a way that you can "eliminate every last cancer cell." There are cancerous cells that can hang out for years and not really do anything, or they can simply follow the life cycle of ordinary cells. Of course, they do have to come from somewhere. Along the way, a healthy cell divides and the offspring either is or becomes cancerous (probably by coming into contact with some carcinogen). So I'm not even sure that elimination completely solves the problem, although no doubt it'll probably help.
Permalink to Comment3. Derek Lowe on May 23, 2005 9:03 AM writes...
The current therapies aren't going to get rid of the cells so much as turn them into a manageable problem. The near-term goal is to turn (some kinds of) cancer into a disease more like diabetes or hypertension: not good news, but something that you can live with if you deal with it properly. I'll be writing more on this during the week. . .
Permalink to Comment4. Sam Jaffe on May 23, 2005 11:18 AM writes...
I disagree that moving away from the classic endpoint model will cost more. In fact, it will be a huge moneysaver for the industry and for the industry as a whole. Choosing an established biomarker as an endpoint for a tiny niche in the cancer market, for instance, will transform the biotech industry. Smaller companies, for instance, can get a much higher chance of approval, albeit with less revenue. But once they've secured approval for something like 'Gleevec-resistant CML', they then have the financial resources to pursue further studies to widen the approved uses of the drug.
Permalink to Comment5. jeet on May 23, 2005 1:20 PM writes...
Genentech has already moved away from "shrinkage" as their primary endpoint towards survival benfit. A hard endpoint, such as death (or in the cardiovascular world an acute event like MI), is treated by the FDA as much stronger data, than are surrogate endpoints.
http://www.gene.com/gene/pipeline/trials/avastin/phase3-pancreatic/index.jsp
http://www.nasdaq.com//aspxcontent/newsstory.aspx?textpath=20050513%5CACQDJON200505131650DOWJONESDJONLINE001105.htm
This is true for most doctors as well. Show them data about tumor shrinkage and most will ask about survival benefit. The same goes for the people making reimbursement/ payment decisions.
Permalink to Comment6. Daniel Newby on May 23, 2005 8:33 PM writes...
I am reminded of the flecainide (Tambocor) debacle. It was observed that heart arrythmias were strongly correlated with post-MI sudden death. The FDA accepted anti-arrythmic efficacy as a surrogate marker for post-MI death rate reduction, the drug was licensed and heavily marketed, and zillions of people started taking it. Alas, several years later a controlled trial showed flecainide users had a hugely increased death rate. (A factor of five if I'm remembering right.) Whoops.
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