In December 2019, just a day after Christmas, Annette Harlow received what turned out to be the final dose of her lung cancer treatment. A few weeks later, sitting in her doctor’s office in Lake Charles, Louisiana, she was given the news that every cancer patient fears: her treatment was no longer working.
“Is that it?” she asked.
“I’m afraid so,” she remembered her doctor replying. “Right now, there’s nothing that we have for you.”
For Harlow, however, that devastating answer did not remain final for long.
The following day, a message appeared on her patient portal. It informed her that if her tumor carried a mutation in a gene known as KRAS, she could be eligible for an experimental clinical trial led by Dr. David Hong in Houston.
The possibility immediately restored her hope. “You could see my spirit just flying in the room. There was something for me,” she recalled.
Tests confirmed that her tumor carried the mutation. Soon, Harlow was regularly making the two-and-a-half-hour journey to the University of Texas M.D. Anderson Cancer Center, where she joined Dr. Hong’s Phase 1 clinical trial.
The experimental treatment was sotorasib, a drug designed to block a mutated form of the KRAS gene. For decades, scientists had regarded KRAS as extremely difficult to target with medicines. Harlow became one of the first patients in the world to receive the new therapy.
More than six years later, the outcome is remarkable. Now in her late 80s, Harlow remains energetic and optimistic, while her cancer continues to be controlled.
“I have had many blessings in life,” she later wrote in an email, “and for sure the two most remarkable ones have been Dr. Hong and sotorasib.”
Her experience illustrates the extraordinary importance of Phase 1 clinical trials.
These trials mark the critical transition between laboratory research and treatment in human patients. Before a new medicine can eventually become available to the wider public, it must first pass through this crucial stage of testing.
Modern medicine has advanced because countless patients have participated in such trials. For people living with advanced cancer, however, their significance is even greater: when established treatments have failed, an experimental therapy may represent one of the few remaining sources of hope.
Dr. David Hong, deputy chair of M.D. Anderson’s Phase 1 program, has spent much of his career working at precisely this intersection between scientific discovery and patient treatment. As one of America’s prominent academic oncologists, his work focuses on taking promising discoveries from laboratories and determining whether they can become effective therapies for patients.
Not every patient experiences the success Harlow did. Yet Hong has witnessed enough apparently hopeless cases respond to experimental treatments to understand how dramatically innovative medicines can alter a patient’s future.
Another example came in August, when the U.S. Food and Drug Administration approved daraxonrasib, a therapy that nearly doubles survival rates for patients with pancreatic cancer, one of the most aggressive and difficult cancers to treat.
Hong led the Phase 1 trial that initially demonstrated the treatment’s potential in humans.
Given such achievements, few people would seem to have greater reason than Hong to feel optimistic about the American system of drug development.
Yet his overriding emotion is concern.
The very clinical-trial system that gave Harlow access to a treatment that extended her life is coming under growing financial pressure.
The cost of conducting clinical trials in the United States has risen dramatically over recent decades. The problem is particularly serious for Phase 1 trials. Since 2017, the average cost of producing the evidence required simply to begin one of these trials has doubled.
For especially complicated therapies, expenses can climb to several million dollars for a single patient.
That creates a troubling paradox. Science is developing increasingly sophisticated ways to fight cancer, but the growing cost of proving that those treatments work may itself become one of the greatest obstacles to getting them to patients.
