Related Experiment Video
Updated: May 21, 2025
Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
Published on: January 29, 2019
Design considerations for randomized comparisons of neoadjuvant-adjuvant versus adjuvant-only cancer immunotherapy
Megan Othus1,2, Elad Sharon3,4, Michael C Wu1,2
1SWOG Cancer Research Network Statistical Center, Seattle, WA, USA.
Abstract:
BackgroundIn 2022, SWOG S1801 was the first trial to demonstrate that single-agent anti-PD-1 checkpoint inhibition used as neoadjuvant-adjuvant therapy leads to significantly improved outcomes compared to adjuvant-only therapy. Endpoints in trials comparing neoadjuvant-adjuvant to adjuvant strategies need special consideration to ensure that event measurement timing is appropriately accounted for in analyses to avoid biased comparisons artificially favoring one arm over another.MethodsThe S1801 trial is used a case study to evaluate the issues involved in selecting endpoints for trials comparing neoadjuvant-adjuvant versus adjuvant-only strategies.ResultsDefinitions and timing of measurement of events is provided. Trial scenarios when recurrence-free versus event-free survival should be used are provided.ConclusionsIn randomized trials comparing neoadjuvant-adjuvant to adjuvant-only strategies, event-free survival endpoints measured from randomization are required for unbiased comparison of the arms. The time at which events can be measured on each arm needs to be carefully considered. If measurement of events occurs at different times on the randomized arms, modified definitions of event-free survival must be used to avoid bias.
Insights
Single-agent anti-PD-1 therapy as neoadjuvant-adjuvant treatment improves outcomes. For unbiased comparison in clinical trials, event-free survival measured from randomization is crucial, especially when event timing differs between treatment arms.
Area of Science:
- Oncology
- Clinical Trial Design
- Immunotherapy
Background:
- SWOG S1801 trial established single-agent anti-PD-1 therapy as effective neoadjuvant-adjuvant treatment.
- Neoadjuvant-adjuvant strategies require careful endpoint selection to prevent biased comparisons.
Purpose of the Study:
- To evaluate endpoint selection for trials comparing neoadjuvant-adjuvant versus adjuvant-only strategies.
- To ensure appropriate accounting for event measurement timing in comparative analyses.
Main Methods:
- Utilized the SWOG S1801 trial as a case study.
- Examined definitions and timing of event measurement for different survival endpoints.
Main Results:
- Provided definitions for recurrence-free survival and event-free survival.
- Outlined trial scenarios for appropriate use of each survival endpoint.
- Highlighted the necessity of event-free survival measured from randomization for unbiased comparisons.
Conclusions:
- Event-free survival measured from randomization is essential for unbiased comparison in neoadjuvant-adjuvant versus adjuvant-only trials.
- Careful consideration of event measurement timing across randomized arms is required.
- Modified event-free survival definitions may be necessary if event measurement times differ between arms to avoid bias.
