Cancer Treatment Pulled: Should The FDA Approval Process Be ‘Tweaked’?

The Food and Drug Administration (FDA) launched its accelerated approval program to bring promising drugs to patient populations who need them most. When a drug is granted an accelerated approval based on compelling early data, continued approval is contingent upon longer-term follow-up data, which can be cause for the indication to be pulled if study goals are not met.

This was recently the case with Tecentriq (atezolizumab) for the treatment of metastatic triple-negative breast cancer (TNBC). Accelerated approval was granted after disease-free survival (time during and after treatment when the patient lives without disease progression) was shown to be improved with atezolizumab in the IMpassion 130 trial. After the drug did not meet the progression-free survival endpoint in the subsequent IMpassion131 trial, Genentech, the manufacturer of the agent, upon conferring with the FDA, decided to voluntarily withdraw its accelerated approval.

“IMPassion130 was the first randomized trial to test a checkpoint inhibitor in triple-negative breast cancer. It showed a clear improvement in progression-free survival in the PD-L1—positive subset of patients, and subsequently demonstrated a benefit in survival as well. Accelerated approval with progression-free survival as opposed to overall survival data was appropriate given the lack of effective therapies for this subtype of breast cancer,” said Dr. Debu Tripathy, a professor of medicine and chair of the department of breast medical oncology at The University of Texas MD Anderson Cancer Center in Houston, in an interview with CURE®.

Since Tecentriq was approved, another checkpoint inhibitor, Keytruda (pembrolizumab) was approved in the TNBC space. “It was generally the conclusion of the those involved that maybe it would be best to go ahead and voluntarily withdraw (Tecentriq), while further supportive studies are being developed,” Tripathy, who is also CURE®’s editor-in-chief, said.

What To Do When a Drug Is Pulled

Patients who are currently receiving a regimen that is no longer FDA approved — such as Tecentriq for metastatic TNBC or bladder cancer or Opdivo (nivolumab) for liver cancer — should talk with their clinicians about what the next best steps are. For some, that may include remaining on the treatment.

“In my opinion, if someone is on that therapy and doing well — that is, they’re not having major side effects and the cancer is not progressing — I think they should stay on it,” Tripathy said.

For a drug to receive FDA approval, the results of a clinical trial must show that it is both safe and effective, and that the benefits exceed the harms.

“However, if (doctors) are evaluating a new patient that is in the need of a new regimen for TNBC, then, of course, we should go with the approved option,” Tripathy explained. “That’s the guidance that I believe we will be receiving, and I think we are going to be hearing more details in the near future.”

Taking a Closer Look

Tripathy said that although he is in favor of keeping the FDA’s option to speed up the approval of a drug, decision makers should take a closer look at what goes into the process.

“In my opinion, we should continue to have the accelerated approval pathway, and we need to learn from these past experiences to see if we should tweak the criteria by which that approval is made,” he said. “The general concept is fine; I think it’s really going to be the judgment on a case-by-case basis when accelerated approvals should be granted. And the criteria may end up getting a little more stringent just on the basis of what we’ve seen.”

The oncology field is “trying to react as quickly as we can” to new biological drugs and rapidly evolving data from clinical trials, Tripathy said. Getting reliable endpoints (the predefined measures and statistical rules that can lead to an approval) and focusing on patient safety should be paramount when pharmaceutical companies are crafting clinical trials.

Drug Development: Trust and Transparency

Many individuals have expressed apprehension regarding the speed at which the COVID-19 vaccine was developed and now with several cancer drug indications being pulled recently, people may become even more wary of the process.

“People are always going to have concerns about how regulatory agencies make decisions, and I think that will always be there — rightfully so. We need to scrutinize this process all the time,” he said.

There are always going to be doubters, but the real issue with trust, according to Tripathy, will surface when entities such as pharmaceutical companies and the FDA start are perceived as withholding information.

“The agencies and the drug companies need to be fully transparent … it’s really when there’s a sense we are not getting the timely and full flow of information that people lose trust. We have to make sure that never happens,” Tripathy concluded. “All we can do is be transparent and true and try to adapt our processes as best as we can to demonstrate that a given trial provides patients with an effective new therapy while protecting them from any harms.”
 

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