Efficacy Endpoints in Oncology Clinical Trials

The following table shows a number of efficacy endpoints. Each of these endpoints is associated with certain advantages and limitations. Although the endpoint definitions provided here are from FDA guidance, please note that individual clinical trials may use different definitions.

Commonly used efficacy endpoints in oncology clinical trials: advantages and limitations1





Overall survival (OS) Time from randomization* until death from any cause
  • Universally accepted measure of direct benefit
  • Easily and precisely measured
  • May require a larger trial population and longer follow-up to show statistical difference between groups
  • May be affected by crossover or subsequent therapies
  • Includes deaths unrelated to cancer
Progression-free survival (PFS) Time from randomization* until disease progression or death
  • Requires small sample size and shorter follow-up time compared with OS
  • Includes measurement of stable disease (SD)
  • Not affected by crossover or subsequent therapies
  • Generally based on objective and quantitative assessment
  • Validation as a surrogate for survival can be difficult in some treatment settings
  • Not precisely measured (ie, measurement may be subject to bias)
  • Definition may vary among trials
  • Requires frequent radiologic or other assessments
  • Requires balanced timing of assessment among treatment arms
Time to progression (TTP) Time from randomization* until objective tumor progression; does not include deaths
Time to treatment failure (TTF) Time from randomization* to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death
  • Useful in settings in which toxicity is potentially as serious as disease progression (eg, allogeneic stem cell transplant)

  • Does not adequately distinguish efficacy from other variables, such as toxicity

Event-free survival (EFS) Time from randomization* to disease progression, death, or discontinuation of treatment for any reason (eg, toxicity, patient preference, or initiation of a new treatment without documented progression)
  • Similar to PFS; may be useful in evaluation of highly toxic therapies

  • Initiation of next therapy is subjective. Generally not encouraged by regulatory agencies because it combines efficacy, toxicity, and patient withdrawal

Time to next treatment (TTNT) Time from end of primary treatment to institution of next therapy
  • For incurable diseases, may provide an endpoint meaningful to patients

  • Not commonly used as a primary endpoint
  • Subject to variability in practice patterns
Objective response rate (ORR) Proportion of patients with reduction in tumor burden of a predefined amount
  • Can be assessed in single-arm trials
  • Requires a smaller population and can be assessed earlier, compared with survival trials
  • Effect is attributable directly to the drug, not the natural history of the disease
  • Not a comprehensive measure of drug activity

Duration of response (DoR) Time from documentation of tumor response to disease progression

*Not all trials are randomized. In nonrandomized trials, time from study enrollment is commonly used.

Oncology Endpoints in a Changing Landscape

The Oncology Endpoints in a Changing Landscape paper is a high-level summary describing the evolution of endpoints in oncology clinical trials and some of the main differences between endpoints.2


  1. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics. http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071590.pdf. Published May, 2007. Accessed February 22, 2016.
  2. Oncology Endpoints in a Changing Landscape. Manag Care. 2016; 1(suppl):1-12.