Oncologists listen when the FDA speaks, even after a drug hits the market
The FDA took off some of the guard rails in an effort to speed innovation. The question was if, once those were gone, there’d be someone to pull the emergency stop when things went wrong.
A new study in JAMA on oncologists and two immunotherapies the FDA restricted after approval suggests the secondary brakes do work. Researchers at the University of Pennsylvania tracked usage rates for two bladder cancer immunotherapies the FDA approved in 2017 but restricted in 2018 after data showed that survival rates were worse in the new therapies than in the standard cisplatin-based chemotherapy. They found that oncologists decreased their usage of the immunotherapy by over 20 percentage points and increased their usage of chemotherapy by over 20 percentage points, suggesting that doctors were closely monitoring FDA updates and adjusting their treatments accordingly.
The therapies were approved through the FDA’s controversial accelerated approval program, based on single-arm Phase II clinical trials as opposed to the full gold-standard Phase III randomized studies. The FDA subsequently restricted the program to patients not eligible for chemo.
“Oncology physicians responded very quickly to an FDA warning and label change for two very popular drugs,” lead author Ravi Parikh told Endpoints News. “What this means is that this is a viable strategy to respond to safety concerns for drugs obtaining accelerated approval in the future. “
Crucially, though, the study does not probe into the costs, in health and dollars, for patients who were given the treatment instead of chemotherapy before the FDA restriction. Nor can it say how many doctors have ignored the FDA warnings or how many patients are still getting the wrong treatment, as the data only look at the overall rates of each treatment and the rate of PD-L1 testing. (The immunotherapies examined are PD1/L1 inhibitors).
The researchers analyzed 1,965 patients between May 2018, one month before the FDA rolled out restrictions, and January 2019. Over that time, the number of patients receiving immunotherapy fell from 51.9% to 30.3% and the rate of chemotherapy increased from 37% to 60.6%. The rate of PD-L1 testing rose from 9.3% to 21.2%.
Nearly 30 years after its launch, the FDA’s accelerated approval program remains controversial, criticized both by those who say it is not fast enough and slows access to experimental treatments for patients who might not live to see the drug hit market, and by those who say increasingly lax standards and a reliance on surrogate endpoints is letting risky and ineffective drugs reach patients.
Two reviews published earlier this year took aim at the program. Another JAMA study found cancer drugs granted accelerated approval were okayed based on less evidence than those approved through the regular process, a BMJ study found studies for surrogate endpoints far more likely to be at risk of bias, and a third JAMA study found only one fifth of cancer drugs approved through AA were later confirmed to improve survival rates.
“Patients don’t need just any cancer drugs, they need cancer drugs that help them have a longer and-or better lives,” Bishal Gyawali, lead author of the latter study, told CNN at the time.
But there is evidence that patients are willing to take the risk because of the hope it provides. A 2017 Value in Health study found that while most physicians would choose a hypothetical safer therapy that offered a guaranteed 4 years of life, no-more-no-less, over a riskier therapy that gave a 20% chance of living more than 7 years but a 50% of not living past year one. Almost 2/3 of patients chose the riskier option.
The study provides a boon to the FDA’s latest project: Facilitate. The project will help physicians submit expanded access requests for individual cancer patients, giving an opportunity for those unable to enroll in a clinical a tether to experimental treatments.