title: Endpoints, patient selection, and biomarkers in the design of clinical trials for cancer vaccines.
abstract: Therapeutic cancer vaccines are an emerging and potentially effective treatment modality. Cancer vaccines are usually very well tolerated, with minimal toxicity compared with chemotherapy. Unlike conventional cytotoxic therapies, immunotherapy does not result in immediate tumor shrinkage but may alter growth rate and thus prolong survival. Multiple randomized controlled trials of various immunotherapeutic agents have shown a delayed separation in Kaplan-Meier survival curves, with no evidence of clinical benefit within the first 6-12 months of vaccine treatment. Overall survival benefit is seen in patients with lower disease burden who are not expected to die within those initial 6-12 months. The concept of improved overall survival without marked initial tumor reduction represents a significant shift from the current paradigms established by standard cytotoxic therapies. Future clinical studies of therapeutic vaccines should enroll patients with either lower tumor burden, more indolent disease or both, and must seek to identify early markers of clinical benefit that may correlate with survival. Until then, improved overall survival is the only clear, discriminatory endpoint for therapeutic vaccines as monotherapies.
authors: Laboratory of Tumor Immunology and Biology and Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Marijo
authors: M
authors: Bilusic
authors: James L
authors: JL
authors: Gulley
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D019496:Cancer Vaccines / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D023381:Endpoint Determination; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019496:Cancer Vaccines