Hacker News Reader

Comment by sjg007 | Hacker News Reader

More importantly, we need FDA regulatory reform. There is absolutely no reason that approved anti-cancer drugs in one cancer type and stage should be limited to just those cases. You should be able to spin up a direct Phase II study without going through Phase I. And more importantly you should be able to get these drugs when all other options are exhausted.

People need to read the book "The Death of Cancer" by the former NCI chief Vincent DeVita. I agree that we need a cancer czar and that the NCI needs to run the show including drug approvals. In addition, academia needs to get with the program.

View on HN

I'm sorry that you think academia isn't "with the program". There's lots of great basic and translational research going on in the academic sphere. Can you at least elaborate, if you're going to paint us all with a broad brush?

Academic cancer centers need to focus on improving clinical outcomes, not just basic research. That cancer centers are associated with primary research institutions universities is largely a compromise between with the NIH and the NCI when the national cancer act was implemented. Tenure is based on basic research publications and on not clinical trials. So therapies are not optimized.

How are we supposed to cure diseases we don't fully understand? How can radical new solutions be tested if we don't even know if they're feasible? Basic research answers these questions.

If you would have waited until you fully understood a disease in order to treat it then kids would still be dying of leukemia today instead of having a 90% remission rate today. People should read about Emil Freireich and the development of chemotherapy.

>"kids would still be dying of leukemia today instead of having a 90% remission rate today"

Do you know a good source for the historical data? I am wondering how they rule out that in the 1950s/60s they saw only much sicker patients, while today a bigger population gets diagnosed and treated. Related, there may be lead time bias: https://en.wikipedia.org/wiki/Lead_time_bias

Any source with discussion of these methodological issues would be helpful.

Where is the money supposed to come from for this? Keeping basic research labs afloat in the current funding environment is hard enough -- clinical trials etc are orders of magnitude more expensive, and not practical for most academics, even those interested in translational research.

For better or worse, our current model is for academics to do basic and early-stage translational research (mostly animal models), then sell/spin off to companies to do the actual trials and reap the profits. I don't see what academics are supposed to do about this.

It would come from contracts from the NCI.

Simply eliminating Phase I is the wrong solution. Entering a Phase II study before Phase I is a great way to maim or kill people. Anti-cancer drugs are often severely toxic; even the new spate of immunocentric therapies proved highly dangerous when first administered. Several early recipients died due to clueless drug administration protocols. THAT's the reason we have Phase I. Humans usually respond differently to a drug than the animals who have gone before.

That said, I think the FDA should approach cancer differently than other diseases, probably by establishing a new experimental model entirely (eliminating the Phase I/II/III system). Given that canger drugs and patients and protocols must ALWAYS be administered sensitively, circumstantially, and adaptively, the current 3 phase system seems to be serving cancer patients poorly, locking them into ineffective treatments for too long, based on too much emphasis on inflexible trial policy. Experimental protocols that are more adaptive and personalized are needed. Of course, this will be very hard technically and insanely expensive clinically.

How to begin this? Like Obama, I'd love to see a 'moon shot' reinvention of the cancer business. Perhaps a project-based redesign of the system is possible, by engaging the most innovative cancer research clinicians and data analysts to explore alternative models for cancer research and drug trials. If that's what Obama has in mind, I support his wish. Now how do we make it work?

I meant in cases where the drug is already FDA approved e.g. Phase I trial has already been completed in other cancer types. There is no need to do another Phase I trial just because it is another cancer type.

The restrictions on using an approved drug for a new cancer type or stage is silly.

The original NCI program for treating Leukemias worked pretty well. The FDA is extremely risk adverse which is not what you want for terminal cancer treatment.

What we need to do is get the price down of cancer drug development. The fundamental problem is cancer is really many diseases so that any targeted drug will only be specific for a very small subset of cancers. This means the market for any new targeted drug is very small and so the ludicrous cost of bring as new drug to market is too great to be supported by the small number of people that will use it.

The cost of these new targeted drugs is basically too high for any healthcare system to support, but the we need to make the drugs even more specific if we are going to get all the cancer types.

Smaller and smaller market with every rising development costs = failure.

> There is absolutely no reason that approved anti-cancer drugs in one cancer type and stage should be limited to just those cases.

Can you expand on that?

Mutations in the BRAF gene, to name one druggable example, are a cause of many different types of cancer - melanoma, some breast, small-cell lung cancer, etc. Under the current paradigm, each type of cancer is treated as a different disease and requires a different clinical trial. This is bad.

What should happen (and is beginning to happen, with "basket trials") is that cancers are grouped by their genetic profile, instead of their tissue of origin. The BRAF V600E mutation is targetable with Vemurafenib, and so that drug should be used regardless of whether you have breast cancer or lung cancer.

Perhaps, but it is also true that these targeted therapies have different success rates among different cancers. Vemurafenib, famously approved for melanoma, hasn't been as successful in papillary thyroid.

Certainly it makes sense to consider genetic profile in treatment, but doesn't the statement "that drug should be used regardless of whether you have breast cancer or lung cancer" ignore the local tumor microenvironment and possible differences in drug resistance expression between cell types, i.e., isn't reducing cancer down to genetic profile alone potentially as problematic as reducing cancer down to its tissue of origin?

Your points are right on - I oversimplified while trying to explain the concept.

This isn't really that much of an issue because oncologists are not always idiots and can prescribe drugs off-label, with cause. Identifying a braf mutant in a disparate cancer type would probably qualify.

It is a huge issue. They risk FDA censure and it usually requires IRB approval as well. It will change with precision medicine but it won't change fast enough. People really need to read DeVita's book. All of my comments are taken from his arguments. DeVita was the chief of the NCI for 30 years.

Reply on news.ycombinator.com