Published On March 28, 2022
Cancer clinical trials are how new treatments get to patients. But in recent years, cries for reform of that system have gotten louder. One significant obstacle is recruitment, as only about 1 in 20 people diagnosed with cancer joins clinical trials, and nearly 40% of clinical trials close without meeting enrollment targets.
In June 2021, the U.S. Food and Drug Administration released a draft of new recommendations designed to expand patient eligibility for clinical trials. Their primary target: people with incurable disease. Historically, most trials have required a cancer patient to try approved treatments before moving on to experimental therapy, even if existing treatments only briefly prolong life. But under the new guidelines, a patient with no avenues to a cure may immediately join a trial for an unproven drug.
Some welcome the new guidance. “In some cases new drugs are the best options for the patient,” says Katherine Arline, chief strategy advisor at Shepherd Foundation, a 501(c)3 committed to driving change for rare cancer patients. Her foundation filed a comment in support of the new guidance, as patients with rare cancers may be particularly likely to benefit, she says.
Others applaud how the new guidance gives patients and their providers greater control of treatment decisions. The FDA guidance recommends that patients be informed about the potential benefits of the new drug, as well as benefits of other available treatments. “Let a smart and consenting patient, together with a conscientious physician, go through that informed consent process and be the main arbiter of who gets on a trial,” says Raymond Osarogiagbon, an oncologist at Baptist Cancer Center in Memphis, Tennessee, who led a recent evaluation of eligibility criteria that was published in Clinical Cancer Research.
Some see increased patient agency as a double-edged sword.
Others, however, see increased patient agency as a double-edged sword. Patients and physicians may be drawn to a clinical trial because the drug is new and unknown, without appreciating the slender chances of success, warns clinical research fellow Mark Lythgoe at Imperial College London. In a review of new cancer drugs receiving FDA accelerated approval, only 20% demonstrated a meaningful benefit in prolonging overall survival in confirmatory trials, he notes.
“Many patients may not be adept at interpreting evidence and making an accurate risk-benefit analysis,” says Lythgoe. For many diagnoses, he says, patients would be equally or more likely to benefit from existing treatments that have already gone through rigorous clinical trials.
With hematologist-oncologist Vinay Prasad at the University of California, San Francisco, Lythgoe recently published two commentaries—in Nature Reviews Clinical Oncology and in the Journal of Cancer Policy—that outline the risks of the new guidance. They worry, for example, that a patient diagnosed with metastatic HER2+ breast cancer might pass up drugs shown to extend life by years in favor of a new drug that has not demonstrated any benefit in humans before.
Lythgoe says he hopes the “appropriate informed consent” process described in the FDA guidance would prevent such scenarios. The FDA, he says, has already made it easier to enroll in cancer trials, most recently through recommendations finalized in July 2020. In that document, patients with brain metastases, who are often excluded because of their poor prognoses, could join more clinical trials.
“That was a step in the right direction,” Lythgoe says. But he believes this newer draft guidance opens the door to potentially worse outcomes. “For me, it needs to have a more established framework, to describe when taking a chance on a new, unproven drug might not be appropriate,” he says.
The comment period for the new guidance closed Aug. 24, 2021, and the FDA has not said when finalized guidance will be published. For many, the change would be a win both for treatment investigations and patients who want to see all of their options. “As a default, everybody should have access to promising trials,” says Osarogiagbon. “For safety or efficacy we can look at excluding this or that type of patient. But then at least it’s a rational clinical choice and not a rule coming down from on high.”
Stay on the frontiers of medicine