There are plenty of cancer drug trials available. The problem: not sufficient patients

Source:   —  August 12, 2017, at 6:25 PM

There are too many experimental cancer drugs in too many clinical trials, and not sufficient patients to test them on.

There are plenty of cancer drug trials available. The problem: not sufficient patients

With the arrival of two revolutionary treatment strategies, immunotherapy and personalized medicine, cancer researchers have found new hope – and a problem that's maybe unprecedented in medical research.

There are too many experimental cancer drugs in too many clinical trials, and not sufficient patients to test them on.

The logjam is caused partly by companies hoping to rush profitable new cancer drugs to market, and partly by the nature of these therapies, which can be spectacularly effective but only in select patients.

In July, an expert panel of the Food and Drug Administration approved a groundbreaking new leukemia treatment, a type of immunotherapy. Companies are scrambling to expand other drugs based on using the immune system itself to attack cancers.

Many of these experimental candidates in trials are quite similar. Yet each drug company wants to have its own proprietary version, seeing a potential windfall if it receives FDA approval.

As a result, there are more than one.000 immunotherapy trials underway, and the no keeps growing. “It’s tough to imagine we can support more than one.000 studies,” said Dr. Daniel Chen, a vice president at Genentech, a biotechnology company.

In a comment in the journal Nature, he and Ira Mellman, also a vice president at the company, wrote that the proliferating trials “have outstripped our progress in understanding the basic underlying science.”

“I think there is a lot of exuberant rush to market,” said Dr. Peter Bach, director of the Middle for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center. “And we're squandering our most precious resource – patients.”

Get melanoma: There are more than 85.000 cases a year in the United States, according to Dr. Norman Sharpless, director of the Lineberger Comprehensive Cancer Middle at the Univ of N Carolina, who was recently named director of the National Cancer Institute.

Most melanomas are cured by surgery, leaving about ten.000 patients who have had relapses and could be candidates for an experimental treatment. But nearly all will be treated by doctors exterior of academic medical centers, who aren't portion of the clinical trials network and so don't proposal patients experimental treatments.

Companies therefore should compete for the few patients with relapsed melanoma who are at centers offering clinical trials. Many finish up struggling to discover sufficient subjects to define whether a treatment actually works – and if so, for whom.

And these drugs often aren't so different from one another.

Immunotherapy drugs that attack a protein known as PD-1 are approved for treatment of lung cancer, renal cell cancer, bladder cancer and Hodgkin’s disease, well-known Dr. Richard Pazdur, director of the FDA’s Oncology Middle of Excellence.

Yet many pharmaceutical companies wish their own anti-PD-1. Companies are hoping to combine immunotherapy drugs with other cancer drugs for added effect, and many don't wish to have to rely on a competitor’s anti-PD-1 drug along with their own secondary drugs.

So in new trials, extra anti-PD-1 drugs are being certified all over again against the same cancers – a me-too business strategy taken to multibillion-dollar extremes.

“How many PD-1 antibodies does Planet Earth need?” wondered Dr. Roy Baynes, a senior vice president at Merck, which received approval for its first such drug in 2014.

Immunotherapy trials have proliferated so quickly that major medical centers are declining to furnish patients to them. The Yale Cancer Middle participates in fewer than 10 % of the immunotherapy trials it's asked to join.

The problem is that many of the trials are uninteresting from a scientific view, said Dr. Roy Herbst, the center’s chief of medical oncology. The companies sponsoring these trials aren't addressing new research questions, he said; they're trying to obtain proprietary drugs approved.

If the struggle to discover patients for immunotherapy trials is challenging, finding patients for another new type of cancer treatment can be following to impossible.

These are drugs that attack mutations that tumors necessity to grow and thrive – targeted therapies. The idea is that tumors can be reliant on certain gene mutations. Obstruct those mutations and the tumors will die.

The problem is that the mutations can be extraordinarily rare. Most patients who have cancers with the mutation in question have number idea; to discover them, large groups of cancer patients must've their tumors genetically tested.

That’s expensive: Genetic sequencing costs about $5.000, and insurers seldom pay. Most cancer patients treated exterior of academic centers don't have their tumors sequenced.

So what to do if you’re a company with a drug that seems to be dramatically effective, but only in a few patients?

You may be forced to undertake a worldwide look for for subjects that can latest for years.

To test a two-drug combination against lung cancer, GlaxoSmithKline searched the United States, Japan, S Korea and Europe for thirteen months just to find fifty-nine patients whose tumors shared a scarce mutation.

It took Pfizer three years to locate fifty lung cancer patients who carried a scarce aberration called ROS1, found in just 1 % of patients.

Clinical trials with patient searches love these are “not for the faint of heart,” said Dr. Mace Rothenberg, a vice president at Pfizer.

It helps that the FDA hasn't insisted on large trials with control groups in instances of targeted therapies with few who qualify.

Instead the agency is looking for drugs with effects so powerful there is number question that they work – studies in which patients went into remission, for example, when all proof suggested they would die.

“We used to have trials not long ago that had seven hundred patients per arm,” Sharpless said, referring to the treatment groups in a study. “That’s nearly undoable now.”

Today, “trials can be eight patients.”

To test a drug that attacks a tumor with a mutation found in just 1 % of cancer patients, researchers at Memorial Sloan Kettering fanned out to the nonacademic medical centers where the majority of patients are treated, offering to pay for most of the cost of genetic testing, seeking patients at practices in the Lehigh Valley of Pennsylvania; Hartford, Connecticut; and Miami.

That's how Bruce Fenstermacher, sixty-seven, a retired long-distance truck driver who lives in Allentown, Pennsylvania, discovered he'd the rare mutation that the drug’s manufacturer, Loxo Oncology, had been looking for.

He'd been receiving immunotherapy for his melanoma, but it'd stopped working and his cancer was spreading again. Discovering that mutation was love hitting the jackpot for Fenstermacher, said Dr. Suresh Nair, an oncologist in private practice in Lehigh Valley.

The experimental drug seems to be working for Fenstermacher. But since so few patients have tumors that might respond, oncologists ponder how they'll find them.

Is it worth it? Is it even possible?

“If, God forbid, I'd a family member with cancer, I'd insist on this type of testing,” said Dr. David Hyman, chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center. “But I don’t know what the rate has to be for society to say, ‘We can’t afford to miss these people.’”

And trials involving Ltd numbers of patients can be perilous. The smaller the study and the shorter its duration, the more likely that what looks love an effect in a trial might simply be a result of chance, Bach of Memorial Sloan Kettering said.

“That leaves some of us proof geeks wondering if it works,” he said.

Some of the new cancer drugs have had such impressive results that their effectiveness wasn't in doubt, said Dr. Vinay Prasad, an oncologist at OR Health and Sciences University.

But, there also were drugs approved without control groups that didn't allow such stunning benefits, and others that markedly slowed the growth of tumors but didn't extend life.

In tiny studies, serious side effects can be missed, said Dr. Scott Ramsey, an oncologist at the Fred Hutchinson Cancer Research Center.

He worries about the expense of the new drugs, including out-of-pocket costs to patients. They may wish the new cancer drugs reaching the market, he said, “but you ponder if you're doing them any favors.”

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