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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