Introduction
Cancer research aims to help patients live longer, healthier lives. But waiting for patients to die to determine how well a drug works tries the patience of doctors and researchers. Measuring the effectiveness of a drug by how long it keeps cancer at bay may offer a faster way to find good interventions, but such methods have their own problems.
Known as progression-free survival (PFS) or the related time to progression (TTP), these methods measure the effectiveness of drugs faster than waiting for study participants to die from their cancers. The U.S. Food and Drug Administration has held meetings to discuss the advantages and pitfalls of PFS (sometimes used as an umbrella term for both concepts). Researchers like PFS because studies can be shorter and smaller, making them potentially less costly. While the FDA appreciates the shorter time it takes to rule therapeutics in or out, it warns that researchers must be careful when using PFS.
"The FDA is demonstrating a flexibility to move towards PFS. We encourage researchers to have a discussion with us about using it as an endpoint," says medical oncologist Richard Pazdur, M.D., director of the FDA's office of oncology drug products. "But it won't replace overall survival. Overall survival is the 'gold standard.'"
The difference between PFS and TTP is mainly in how deaths are tallied. PFS measures the time that patients live without their cancer getting worse, from some arbitrary starting point, often the date of the intervention. Since survival is measured (as the name suggests), deaths such as those from drug toxicity or unrelated accidents are included in the final count. TTP measures the time from the arbitrary start date until the patient progresses, but deaths are not included of the TTP equation. In either case, overall survival often is measured along with the PFS and TTP endpoints.
"I prefer PFS because it is a better surrogate for overall survival," says hematologist Kyle Robert, M.D., of the Mayo Clinic in Rochester, Minn. "If you have an effective treatment, but half the patients died because of the toxicity, then you could have a nice, long TTP, but half would be dead," Robert says.
Some researchers prefer the shorter endpoint over the long wait. "PFS is cleaner than overall survival," says statistician Karla Ballman, Ph.D., also of the Mayo Clinic. "If patients progress, they can go off the protocol and get treated by a doctor. If you have a survival endpoint, you don't know how people got treated outside of the trial, and other factors might contribute to their survival or death."
However, perhaps the biggest stumbling block is measuring success, says biostatistician Katherine Panageas, Dr.P.H., of Memorial Sloan-Kettering Cancer Center in New York. "People are much more subjective in assessing progression as opposed to death."