Chemotherapy and radiation failed to thwart Erika Hurwitz’s rare cancer of white blood cells. So her doctors offered her another option, a drug for melanoma. The result was astonishing.
Within four weeks, a red rash covering her body, so painful she had required a narcotic patch and the painkiller OxyContin, had vanished. Her cancer was undetectable.
“It has been a miracle drug,” said Mrs. Hurwitz, 78, of Westchester County.
She
is part of a new national effort to try to treat cancer based not on
what organ it started in, but on what mutations drive its growth.
Cancers
often tend to be fueled by changes in genes, or mutations, that make
cells grow and spread to other parts of the body. There are now an
increasing number of drugs that block mutations in cancer genes and can
halt a tumor’s growth.
While
such an approach has worked in a few isolated cases, those cases cannot
reveal whether other patients with the same mutation would have a
similar experience.
Now, medical facilities like Memorial Sloan Kettering Cancer Center
in New York, where Mrs. Hurwitz is a patient, are starting coordinated
efforts to find answers. And this spring, a federally funded national
program will start to screen tumors in thousands of patients to see
which might be attacked by any of at least a dozen new drugs. Those
whose tumors have mutations that can be attacked will be given the
drugs.
The
studies of this new method, called basket studies because they lump
together different kinds of cancer, are revolutionary, much smaller than
the usual studies, and without control groups of patients who for
comparison’s sake receive standard treatment.
Researchers and drug companies asked the Food and Drug Administration for its opinion, realizing that if the F.D.A. did not accept the studies, no drugs would ever be approved on the basis of them. But the F.D.A. said it sanctioned them and could approve drugs with basket study data alone.
Instead
of insisting on traditional studies, said Dr. Richard Pazdur, who
directs the F.D.A. office that approves new cancer drugs, the agency
will look at the data and ask, “Is the American population going to be
better off with this drug than without it?”
These
are the sorts of studies many seriously ill patients have been craving —
a guarantee that if they enter a study they will get a promising new
drug. And the studies move fast; it does not take years to see a big
effect if there is one at all.
In
Mrs. Hurwitz’s case, the mutation in her rare cancer is in a gene,
BRAF, found in about 50 percent of melanomas but rare in other cancers.
She is among dozens of patients with the same mutation, but different
cancers, in the new study that gives everyone the melanoma drug that attacks the mutation.
Basket
studies became possible only recently, when gene sequencing became so
good and its price so low that doctors could routinely look for 50, 60
or more known cancer-causing mutations in tumors. At the same time, more
and more drugs were being developed to attack those mutations. So even
if, as often happens, only a small percentage of patients with a
particular tumor type have a particular mutation, it was possible to
find a few dozen patients or more for a clinical trial by grouping
everyone with that mutation together.
In
a way, this is a leading edge of precision medicine that aims to target
the drug to the patient. Unlike previous efforts that looked for small
differences between a new treatment and an older one, with basket
studies, researchers are gambling on finding huge effects.
“This
is really a new breed of study,” said Dr. David Hyman, a cancer
specialist at Memorial Sloan Kettering who directs the study Mrs.
Hurwitz is in and two similar ones.
And
they are seeing some unprecedented responses, along with some failures.
The responses, though, can be so striking that control groups might be
unwarranted or infeasible, Dr. Pazdur said.
“Conventional
therapy might give a response rate of 10 or 20 percent,” Dr. Pazdur
said. “The newer drug has a response rate of 50 or 60 percent. Does it
make sense to do a randomized trial?” And even if a trial were planned,
he said: “Who would go on that trial? Would you go on that trial?”
“When
you are having a big effect, it is kind of jaw dropping,” Dr. Pazdur
added. “These are response rates we haven’t seen before in diseases.”
But
these are still the early days, researchers caution. “It is a different
world we are walking into,” said Dr. Daniel Costa, a lung cancer
researcher at Beth Israel Deaconess Medical Center in Boston. “And we are learning as we go along.”
The
new studies pose new problems. With no control groups, the effect has
to be enormous and unmistakable to show it is not occurring by chance.
When everyone gets a drug, it can be hard to know if a side effect is
from the drug, a cancer or another disease. And gene mutations can be so
rare that patients for a basket study are difficult to find.
The rarity of the mutations, in fact, is one reason for the new national effort, supported by the National Cancer Institute. Its study, called Match,
is essentially a basket of basket studies. Doctors around the country
will be sending tumor samples from at least 3,000 patients to central
labs that will examine them for mutations. Those with any of a dozen or
so mutations in their tumors can enroll in studies of drugs that target
their tumor’s mutation.
Dr. Keith Flaherty of Massachusetts General Hospital,
principal investigator for the Match trial, said the number of baskets
was uncertain — it would depend on the number of drugs. But he expects
12 to 15 baskets to start, expanding to perhaps 40 or more. There will
be 31 patients per drug.
He
anticipates mixed results. “We are exploring an unknown space here,”
Dr. Flaherty said. “But it is essentially impossible for this whole set
of baskets to fail.”
To
show what is possible, Dr. José Baselga of Memorial Sloan Kettering
points to preliminary results he presented in December for the basket
study that includes Mrs. Hurwitz.
Among 70 patients, there are eight types of cancer. Eighteen patients had one of two very rare cancers, Erdheim-Chester disease or Langerhans
disease, the cancer that struck Mrs. Hurwitz. Of them, 14 responded to
the melanoma drug — their tumors vanished, shrank or stopped growing —
and the remaining four have not been taking the drug long enough to say.
“Unbelievable,” Dr. Baselga said.
“This
is working in a way that is clear, that is unprecedented,” he said. “I
don’t have enough patients to do a Phase 3 study,” he added, referring
to the large, randomized study traditionally used to test new drugs,
“and I even question the morality of it.”
But others in basket studies have not fared so well.
Eleni Vavas entered a basket study at Memorial Sloan Kettering hoping to stop the stomach cancer
that was killing her. The study, said her husband, John Vavas, “was our
last-ditch, Hail Mary effort.” His wife, who was 36, entered it last
spring, the only patient with stomach cancer. But, Mr. Vavas said, “she just didn’t respond.”
She died on July 1.
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