End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival?
Gill S, Sargent D
Oncologist. 2006 Jun; 11(6):624-9
The FDA defines disease-free survival (DFS) is defined as “the time from randomization until recurrence of tumor or death from any cause” (FDA 2007). According to the FDA, “Although overall survival is a conventional endpoint for most adjuvant settings, DFS can be an important endpoint in situations where survival may be prolonged, making a survival endpoint impractical.” (FDA 2007). DFS needs to be evaluated carefully — a patient’s quality of life (QOL) in the period of extended survival is an important consideration for payers, providers, and patients alike (Gill 2006).
DFS often is used as a surrogate for OS in which recurrence of the disease represents a major reason for death in the treated population. In such cases, therapies used to treat cancer recurrencemay prolong survival but are unlikely to result in a cure. DFS is particularly appropriate when the interval between recurrence and death is lengthy and would otherwise require a longer follow-up for evaluation of OS (Gill 2006).
Recurrences between episodes of breast cancer, for instance, may be measured in years. As breast cancer is the second-leading cause of cancer-related deaths in women (ACS 2008), recent research has focused on potential cures. Between 20 and 30 percent of all metastatic breast cancer cases overexpress a protein called HER2. Patients with HER2 overexpressing tumors generally have faster tumor growth, a greater chance of relapse, and a reduced chance of long-term survival (Vogel 2005, Neyt 2006).