Do patients with advanced cancer value progression-free survival as a cancer treatment end point?
This systematic review qualitatively assessed 17 articles representing 3646 patients with advanced cancer that evaluated their understanding, preferences, and values toward progression-free survival as a treatment end point. However, heterogeneity of methods, attribute selection, and definitions of progression-free survival given to patients across the studies limited the ability to interpret the results.
High-quality studies are needed that clearly define progression-free survival for patients with advanced cancer and systematically document their understanding of the term to assess whether progression-free survival is of value to them.
It is unclear whether patients with advanced cancer value surrogate end points, particularly progression-free survival (PFS). Despite this uncertainty, surrogate end points form the basis of regulatory approval for the majority of new cancer treatments.
To summarize and qualitatively assess studies evaluating whether patients with advanced cancer understand and value PFS.
MEDLINE, Embase, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature databases were searched from database inception to November 12, 2018. Articles eligible for inclusion investigated patient understanding, preference, or perceived value of disease progression or PFS in the setting of advanced cancer. Three authors independently reviewed and extracted data from all studies eligible for inclusion.
In total, 17 studies representing 3646 patients were included. Of these studies, 15 specifically aimed to assess patients’ values toward, and their willingness to trade off toxic effects for gains or losses in the end point of PFS. All studies examined used widely disparate definitions when attempting to describe the meaning of PFS to patients. Ten studies specifically presented patients with the term progression-free survival as an attribute choice. In the words used to define the attribute of PFS, 6 studies used the term survival. Five studies clarified that PFS may not translate into better overall survival, and 5 studies explained that improvements in PFS may not reflect how well the patient may feel. No study clarified that a PFS event could represent either progression or death, and no study defined for the patient what constituted progression. The studies assessed herein underrepresented ethnic and racial minorities (mean percentage of white patients, 88%; range, 77%-96%). Values and preferences may vary across cultural backgrounds given that different relative preferences were assigned to cost and efficacy outcomes in North American vs Asian studies, although only a few studies were evaluated.
Conclusions and Relevance
The existing literature evaluating patients’ understanding, preferences, and values toward the end point of PFS was severely limited by the heterogeneity of methods, attribute selection, and descriptions used to define PFS to patients. High-quality studies are needed that clearly define PFS for patients and that systematically document their understanding of the term. Only then can it be assessed whether PFS is an end point of value to patients with advanced cancer.
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:https://doi.org/10.1001/jamaoncol.2019.3338
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