Biotechnology Healthcare - June 2008 - (Page 24) An endpoint such as disease-free survival may give patients access to effective therapy sooner — potentially saving lives while reducing long-term costs. clinical relevance to patients (FDA 2007, Gill 2006). For payers, OS provides the most objective measurement of how efficacious an oncology agent is. Overall survival is an endpoint that takes time to evaluate in full, requiring relatively large and lengthy clinical trials. It also includes noncancer deaths, particularly in larger or older populations, that may skew the study (FDA 2007). With disease states such as metastatic breast cancer, where chemotherapy regimens are often rotated, it can be difficult to determine which regimen contributed to OS. Moreover, when first approved, a product may not have OS data. Payers must be vigilant in evaluating the data from postlaunch trials to accurately assess OS benefit. Disease-free survival. The FDA defines disease-free survival (DFS) is defined as “the time from ranFIGURE 2 domization 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 recurrence may prolong survival but are unlikely to result in a cure. DFS is particularly appropriate when the interval between re- Median survival time 100 Percent still alive 75 50 25 0 0 12 Time in months 24 36 The dotted line indicates the median survival time, or the time at which 50 percent of the patients are still alive. Source: Motulsky 1995; adapted with permission currence 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). Trastuzumab (Herceptin), a humanized monoclonal antibody that targets the HER2 receptor, is approved for the treatment of HER2 overexpressing breast cancer (Neyt 2006). The Herceptin Adjuvant (HERA) clinical trial measured DFS as the primary endpoint; other endpoints included OS, time to recurrence, time to distant recurrence, overall safety, and cardiac safety (Piccart-Gebhart 2005). The HERA trial had an external independent data monitoring committee, the primary role of which was to monitor safety data and advise the trial’s steering committee about the release of trial results (HERA 2006). A planned interim efficacy analysis was published in 2005 and included 475 events (Piccart-Gebhart 2005). OS results had not yet reached statistical significance at the time of publication, underscoring the need for a surrogate endpoint, such as Tables, pages 25, 26; article continues on page 32 24 BIOTECHNOLOGY HEALTHCARE · MAY/JUNE 2008
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.