Postmarketing Analysis of Sipuleucel-T—The Importance of Real-World Data
Authors: Alice C. Fan, John T. Leppert
Journal: JAMA Network Open (2019)

Sipuleucel-T was the first autologous cellular immunotherapy approved by the US Food and Drug Administration (FDA) in 2010 and is used in the treatment of patients with metastatic castrationresistant prostate cancer. 1 Sipuleucel-T demonstrated a 4-month overall survival benefit for patients with asymptomatic or minimally symptomatic disease in a randomized clinical trial. 1 Dores et al 2 analyze reports to the FDA's Adverse Event Reporting System to examine adverse events in patients who have received sipuleucel-T as reported by health care professionals, consumers, and manufacturers.This postmarketing analysis identified several adverse events that were more common among patients receiving sipuleucel-T compared with all other patients in the database, confirming important adverse events described in the initial clinical trials and package materials.These include infusion-related reactions, infections, and thromboembolic events.Dores et al 2 provide additional evidence that sipuleucel-T is generally safe and is not associated with previously unrecognized adverse events.Understanding the safety profile of sipuleucel-T is critically relevant to the care of patients with metastatic castration-resistant prostate cancer.The potential risks and long-term adverse events associated with sipuleucel-T are not well known, because sipuleucel-T is the first autologous cellular immunotherapy, it was approved less than a decade ago, and only 1 in 10 patients with metastatic castration-resistant prostate cancer receive sipuleucel-T. 3Consequently, few practices will have enough experience to recognize and attribute rare complications to this novel therapy.The FDA's Adverse Event Reporting System serves as an important resource to gather real-world safety experience and outcomes of patients receiving sipuleucel-T.Although an overall survival benefit was seen in clinical trials, 1 sipuleucel-T treatment is rarely associated with significant changes in prostate-specific antigen levels, in the radiographic assessment of tumor burden, or in progression-free survival. 4Without reliable biomarkers or surrogate outcome measures, clinicians rely on patient characteristics to identify appropriate patients.Therefore, understanding patterns of serious adverse events using real-world data will provide additional information to identify patients who are best suited for sipuleucel-T.For example, infections were reported disproportionately in patients receiving sipuleucel-T. 2If central venous catheter use can be avoided, perhaps complications such as line infections can also be decreased.In addition, patients at high risk for thromboembolic events or with multiple risk factors for cerebrovascular or myocardial events may not be ideal candidates for sipuleucel-T.Further reports from the Provenge Registry for Observation, Collection, and Evaluation of Experience Data (PROCEED) 5,6 are also expected to help optimize patient selection.Postmarketing analysis may also inform sequencing strategies for patients with metastatic castration-resistant prostate cancer.Since 2010, additional agents such as cabazitaxel, abiraterone, enzalutamide, and radium 223 dichloride have been approved by the FDA.Sipuleucel-T was approved on the basis of efficacy data in patients with asymptomatic or minimally symptomatic disease.It is notable that in the FDA's Adverse Event Reporting System, 128 patients died within 30 days of infusion. 2In contrast, less than 1% of patients died within 30 days in the preapproval clinical trials. 1 This highlights significant differences in the use of sipuleucel-T outside of clinical trials.For the 35.6% of these deaths in the FDA's Adverse Event Reporting System that were attributed to prostate cancer, patients received the drug too late to derive benefit. 2 Sipuleucel-T would ideally be