LAUSR

The use of various surrogate end points in cancer clinical trials is erupting. Such measures reflect the efficacy of a studied intervention and may form the basis of a future approval by the United States Food and Drug Administration (FDA) or European Medicines Agency. Nevertheless, the definition of different surrogate end points may be difficult to assimilate by medical providers and/or patients. Patients’ default thinking of a good cancer treatment is the one that will result in either cure, prolonged survival, or better symptom control (i.e. quality of life (QoL)). Progression-free survival (PFS), a common surrogate end point, is usually used to reflect a possible overall survival (OS) or QoL benefit. The use of PFS can be misleading to patients because it has the survival wording and because many of them will not understand the meaning of such measure especially in advanced/metastatic cancers (1,2). As an example, the definition of response may rely on computed tomography as a tool to assess cancer response to a given intervention, however, its use can be associated with measurement errors related to a specific cancer characteristics or treatment effect. There is incremental use of different surrogate end points by FDA to approve cancer medications in the last two decades. The FDA ’s role is centered around allowing access to what is likely to help cancer patients based on a given data. Almost one-third of the approvals were based on surrogate end points that were used for the first time in a specific cancer setting (3). Those surrogate markers that resulted in a subsequent FDA approval have different definitions that may not align with patients and clinicians’ expectations. PFS is defined in multiple ways according to different reporting methodologies. Median PFS, which is usually measured in months, resembles the time point where half of the studied patients either will have worsening of their cancer (i.e. progression) or will die. A time point PFS analysis (e.g. 6months PFS, 12months PFS, etc.) usually reflects the percentage of patients with cancer progression or who will die at a specific time of measurement (4). Other methods include reporting a ratio of patients with either progression or death as PFS hazard ratio. All of those measures are subject to assessment bias secondary to the measurement tools and the frequency of measurement. This bias is most evident when using one methodology instead of using all of them. It is exceedingly important for medical providers to understand the differences between such measures and to explain to patients what they mean. Worsening (progression) of cancer may have different meanings: for medical providers, it usually means a specific growth of a mass on an imaging modality or worsening of a measured disease variable on a blood test or other specific test. For patients, such measures may be meaningless especially when they do not translate into OS or QoL benefits. There will be no patient benefit of a shrinkage of metastatic colon cancer mass from 5 to 3 cm if the patient is still feeling the same and living for the same length of time without treatment. Such imaging improvement may not necessarily mean better patient