March 5, 2015

Revolutionary, Mutation-Driven "Basket" Studies Give Cancer Patients Quicker Access to Experimental Drugs

In its effort through the years to find cures for cancer, the medical community quite naturally focused on cancer types. There were trials for drugs to treat lung cancer, different trials for drugs to treat breast cancer, still others for colon cancer. The approach made sense, especially in the absence of other research options.

Now, because science has advanced so dramatically, and as “individualized” medicine therefore becomes more and more possible, researchers are testing drugs that specifically attack cancer-causing cell mutations. Their work has already identified about 60 different cancer-causing mutations in various tumor types.

The very same mutations in particular genes might appear in different types of cancer, which means test subjects for the very same experimental drugs might be battling stomach cancer, or esophagheal cancer, lung cancer, skin cancer, etc.

This spring, a federally funded national program will screen tumors in thousands of cancer patients to determine which might be attacked by any of the new drugs. If their tumors show mutations that might be targeted, patients eager for experimental treatment will get it.

New "Basket" Studies
These revolutionary trials are called “basket studies” because they lump together various cancers. They’re smaller than more typical studies, and they don’t include control groups of people who would receive standard treatments to make comparisons possible.

In the older trial model, researchers looked for small differences between an older treatment and a newer one. Now, with these basket studies, researchers are gambling to find very dramatic results… results so impressive that control groups might be superfluous.

 Dr. David Hyman, a cancer specialist at Memorial Sloan Kettering, said:
This is really a new breed of study. Conventional therapy might give a response rate of 10 or 20 percent. The newer drug has a response rate of 50 or 60 percent. Does it make sense to do a randomized trial? When you are having a big effect, it is kind of jaw dropping. These are response rates we haven’t seen before in diseases.

Still, the basket study approach presents its own challenges. Since there aren’t control groups, the effect of any experimental drugs must be “enormous and unmistakable” to demonstrate that the results have not occurred by chance. 

And because all participants receive the same drug, it’s challenging to assign causes for side effects. Are they happening because of the drug, the cancer, another disease, something else?

"Match" -- the Basket of All Baskets
Another challenge is that some tumor mutations are very rare, which is one reason the new national effort is underway. Called “Match” (Molecular Analysis for Therapy Choice), it is supported by the National Cancer Institute and is fundamentally a basket of basket studies.

From across the country, doctors will send tumor samples from over 3,000 patients -- whose tumors no longer respond to standard therapy and continue to grow -- to central labs, where scientists will examine them for mutations. Then, patients whose cancers show any of the identified mutations can sign up for the particular study that targets their tumor’s unique mutation.

Dr. Keith Flaherty of Massachusetts General Hospital, principal investigator for the Match trial, expects to have about 15 baskets to start, and that number might grow to 40 or beyond, depending on the number of drugs developed. He said, “We are exploring an unknown space here. But it is essentially impossible for this whole set of baskets to fail.”

Will the FDA Support Basket Study Results?
A key question in this new realm of un-randomized basket studies: How will the FDA react to the results? Will the agency approve drugs based on small trials for which there were no control groups?

Several weeks ago, I ran a post about the FDA’s new willingness to make experimental drugs available to sick and dying people for whom no other options were available. The FDA has taken the same position here, indicating it would approve drugs based on basket study data alone.

Dr. Richard Pazdur directs the FDA office that approves new cancer drugs. His explanation? “Is the American population going to be better off with this drug than without it?”

He apparently thinks we will.

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There’s been lots of coverage about these new basket studies, and about “Match,” the basket study of basket studies supported by the National Cancer Institute.

Here's the National Cancer Institute's summary, which was updated on March 2.

A key source here was an article that appeared in the February 25 edition of The New York Times.

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