Rethinking FDA Metrics for Immuno-Oncology Agents

Immunotherapy is transforming how cancer is treated, offering the potential for long-term survival in diseases that were once considered uniformly fatal. But according to one leading expert, the way these therapies are evaluated has not kept pace with the science, raising concerns that patients may be waiting longer than necessary to access life-extending treatments.

In the discussion, Richard Goldberg, MD, a gastrointestinal oncologist at the WVU Cancer Institute, highlighted a fundamental disconnect between how newer immunotherapies work and how regulators, particularly the FDA, continue to evaluate them.

Goldberg explained that traditional chemotherapy and immunotherapy operate through entirely different mechanisms. Cytotoxic chemotherapy delivers a high concentration of drug that rapidly kills tumor cells if they are sensitive to treatment. The effects, however, are often short-lived, and response is typically measured by how quickly and significantly tumors shrink.

Immunotherapy, by contrast, activates the body’s immune system to recognize and attack cancer cells, a process that can take time and may not produce immediate or straightforward tumor shrinkage. In some cases, tumors may initially appear to grow before shrinking, a phenomenon known as “pseudo-progression.” Despite this well-documented effect, Goldberg argued that regulatory frameworks still rely heavily on metrics developed during the chemotherapy era.

“Using just overall response rate as a metric for accelerated approval and its ability to predict overall survival is, in my mind, a flawed metric,” Goldberg said, noting that imaging changes alone may not fully capture the benefit of immunotherapy.

This reliance on traditional end points such as overall response rate could have real consequences for patients. While chemotherapy in advanced, noncurative settings rarely leads to long-term survival, immunotherapy has changed that paradigm. Some patients treated with immuno-oncology agents are now living a decade or longer, outcomes that would have been exceedingly rare in the past.

Goldberg emphasized that evaluating survival over longer intervals may be more meaningful. “With chemotherapy drugs in the setting of advanced disease, where it’s noncurative, nobody’s alive at 10 years, but with immuno-oncology agents, people are alive at 10 years,” he said. “Looking at survival at intervals makes a difference. And of course, what matters to patients is survival.”

The implications extend beyond clinical nuance to regulatory decision-making. As concerns grow about delays in the drug approval process, Goldberg pointed to emerging survival data that he believes should carry greater weight. “When you’re getting a 40% rate of survival at 2 years, that’s important,” he said, adding that such outcomes should be more heavily considered by regulators.

The debate reflects a broader tension in oncology: how to balance the need for rigorous, standardized evaluation with the rapidly evolving nature of cancer therapeutics. As immunotherapy continues to reshape expectations for long-term survival, experts like Goldberg are calling for a reassessment of the metrics used to define success.

Ultimately, the question remains whether regulatory frameworks will evolve alongside scientific innovation, or risk slowing the delivery of treatments that could meaningfully extend patients’ lives.