A new study questions the clinical benefits of the Food and Drug Administration's accelerated approval program, which provides cancer patients access to new drugs faster.
A team of researchers evaluated 93 cancer drugs that were given permission to be marketed early based on promising preliminary studies. They found that only 19 of those drugs clearly extended patients' lives in subsequent confirmatory trials.
They published their findings in the journal JAMA Internal Medicine.
Patients Get Little Benefit From Accelerated Approval Program
Some cancer treatment drugs that received accelerated approval from the FDA but failed to improve overall patient survival in confirmatory trials are bevacizumab, atezolizumab, nivolumab, and pembrolizumab.
Bevacizumab, for example, was granted accelerated approval as treatment for glioblastoma, an aggressive brain cancer. The drug did not improve survival or the quality of life of the patients who took it. However, the FDA left it on the market.
Moreover, the researchers discovered that the subsequent confirmatory trials made after approval did not use overall survival rate or improvement in the quality of life as benchmarks. Instead, they used "surrogate endpoints," a way to measure the impact of a drug without waiting for real clinical data.
For example, the subsequent confirmatory trial might not prove the ability of a drug to improve the patients' quality of life or their overall survival but many saw their tumors shrink. The surrogate endpoints are much easier and much faster to assess.
"So the confirmatory trials were not confirming clinical benefit but actually confirming benefit in a surrogate endpoint," Bishal Gyawali, a professor at Queen's University in Canada and the first author of the study, told CNN. "The major takeaway is that for drugs approved on the basis of accelerated approval pathway, only a minority have proven clinical benefit and most drugs just demonstrate benefit in surrogate endpoints in the confirmatory trials."
In response, Amanda Turney, a spokesperson for the FDA, sent an e-mail to CNN, explaining that the agency only approved drugs based on a "favorable risk-benefit profile."
"We have had multiple discussions over a number of years within the global scientific and patient community, including with the Oncologic Drugs Advisory Committee, regarding the use of progression-free survival, response rate, and other endpoints to support approval of drugs that treat cancer," reads the statement. "It has been widely accepted that benefit can be demonstrated by a number of endpoints, not just overall survival."
Improving The Process
The researchers clarified that the study was not meant to criticize the FDA. Gyawali recommended that the confirmatory studies must be conducted in time and use clinical endpoints, such as survival rate and improvement in the quality of life, to determine clinical benefits.
The team also admitted that the study has its limitations. The status of confirmatory trials, for example, are constantly changing. The researchers also relied on reported results and used publicly available data.