Patients with cancer may not understand the meaning of progression-free survival (PFS), according to the results of a study recently published in JAMA Oncology. As a result, the value a patient places on PFS is unknown.
“I'm not surprised to see their conclusion at all,” said Feng Xie, PhD, professor of health economics in the department of health research methods, evidence, and impact at McMaster University in Ontario, Canada, who was not involved in the study, during an interview with CancerNetwork®.
“When it comes to the [meaning of] PFS, not everyone can understand exactly what PFS means to them because, as the name implies, it seems that it has something to do with survival,” said Xie. Xie added that in reality, it might have nothing to do with survival.
The systematic review included 17 studies from the published literature that evaluated patient understanding, preference, or perceived value of disease progression or PFS among patients with advanced cancer. Collectively, these 17 studies represented 3646 patients with advanced cancer, the majority of whom were white (mean, 88%; range, 77% to 96%).
A review of the studies revealed that, when conveying the meaning of PFS, all of them used considerably different definitions of PFS. When defining PFS to patients, 6 studies included “survival” in the definition, 5 stated that a PFS benefit may not lead to an overall survival (OS) benefit, and 5 stated that a PFS benefit may not reflect how well a patient feels.
For studies that allowed patients to rank the importance of attributes, such as OS, PFS, and adverse events, OS was always ranked as the most important attribute when presented as an option. Only when OS was not an option was PFS ranked as the most important attribute to patients. To Xie, this finding indicates that people “really don't understand” what PFS means.
Beyond this, the study raises additional concerns about the use of PFS in clinical trials. The authors pointed out radiologic progression was initially defined as a way to “describe changes in tumor size in response to therapy to aid in identifying signals of activity in early drug development,” but was “never intended to infer a clinically meaningful benefit.”
Xie agreed, explaining that PFS has been “gradually” used as secondary outcome measures and is now “pretty much standard” as primary outcome measures in “many” oncology clinical trials. In fact, a study found that PFS or time to progression were never used as primary endpoints in oncology randomized clinical trials between 1975 and 1984. Then its popularity grew. Between 1984 and 1994, PFS and time to progression were used in 2% of trials and then in 26% of trials between 2005 and 2009.
Another issue the study raises is the validity of PFS as a surrogate endpoint in cancer trials because while PFS has been shown to be a valid surrogate endpoint for OS for certain cancers, for most, the translated OS benefit remains an assumption.
“We don’t have really strong evidence to show that it is a good, valid surrogate for overall survival or health-related quality of life, two key end points that are valuable to cancer patients,” said Xie. Moving forward, Xie said the issue needs to be examined in 2 ways. First is how to improve communication with the patient about what PFS is, and second is how the efficacy of a new treatment should be evaluated.
Raphael MJ, Robinson A, Booth CM, et al. The Value of Progression-Free Survival as a Treatment End Point Among Patients With Advanced Cancer: A Systematic Review and Qualitative Assessment of the Literature. JAMA Oncol. Published online September 26, 2019. doi:10.1001/jamaoncol.2019.3338