Endpoints Based on Survival
Overall survival
Overall survival is defined as the time from randomization until death from any cause and is measured in the intent-to-treat population.
Endpoints Based on Tumor Assessments
In many cancer types, radiographic tumor assessments directly measure components of the disease, and tumor measures commonly trigger treatment decisions in clinical practice. Therefore, tumor measure based endpoints are considered more clinically relevant than other biomarkers. Tumor measure based endpoints may support either traditional (as a clinical endpoint that represents clinical benefit or a surrogate endpoint for traditional approval) or accelerated approval and include DFS (and EFS), ORR, CR, TTP, and PFS.
Disease-Free Survival (and Event-Free Survival)[DFS&EFS]
DFS is defined as the time from randomization until disease recurrence or death from any cause. EFS is defined as time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, or death due to any cause.
- Treatment effect measured by DFS or EFS can be a surrogate endpoint to support accelerated approval, a surrogate endpoint to support traditional approval.
Objective Response Rate(ORR)
ORR is defined as the proportion of patients with tumor size reduction of a predefined amount
and for a minimum time period.
Complete Response(CR)
CR is defined as no detectable evidence of tumor. CR is generally measured through imaging studies (e.g., CT scans) or through histopathologic assessment (e.g., bone marrow biopsy or breast cancer resection specimens).
- Treatment effect measured by CR can be a surrogate endpoint to support accelerated approval, a surrogate endpoint to support traditional approval.
Time to Progression and Progression-Free Survival (TTP & PFS)
TTP is defined as the time from randomization until objective tumor progression; TTP does not include deaths. PFS is defined as the time from randomization until objective tumor progression or death, whichever occurs first.
- TTP and PFS have served as primary endpoints for drug approval.
Time to Treatment Failure(TTF)
TTF is defined as a composite endpoint measuring time from randomization to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death.
- TTF is generally not recommended as a regulatory endpoint for new molecular entity drug approval.
Endpoints Involving Symptom Assessment
Symptomatic improvement is considered a clinical benefit. FDA drug approvals have used patient symptom assessments and/or physical signs representing symptomatic improvement (e.g.,weight gain, decreased effusion) as an important efficacy endpoint.
Specific Symptom Endpoints
- Symptom improvement/palliation is a direct measure of clinical benefit rather than a surrogate endpoint.
- Time to progression of cancer symptoms, an endpoint similar to TTP, is also a direct measure of clinical benefit rather than a potential surrogate endpoint.
- composite symptom endpoint or symptom scale should have components of similar clinical importance and an analysis of the contribution of the components should be submitted with the primary analysis of the overall composite endpoint.
