General and statistical hierarchy of appropriate biologic endpoints.
The introduction of newer classes of chemotherapeutic agents, with varying mechanisms of action by which they affect tumor growth and viability, has challenged the traditional norms of clinical trial design and drug approval in oncology. Most notably, the emergence of cytostatic biologic agents with antitumor efficacy has necessitated reassessment of appropriate primary endpoints for phase II and III trials in advanced disease from both a clinical and regulatory standpoint. Recent data in the field establishes an endpoint hierarchy, which places progression-free survival (PFS) between overall survival (OS) and response rate (RR) as appropriate primary endpoints for assessing the clinical efficacy of cytostatic and cytotoxic agents.
Sargent
Daniel
D
Cancer Center Statistics, Mayo Clinic, Rochester, Minnesota 55905, USA. Sargent.Daniel@mayo.edu
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D018572:Disease-Free Survival; D017277:Drug Approval; D023381:Endpoint Determination; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015415:Biomarkers