Phase I and Phase II Objective Response Rates are Correlated in Pediatric Cancer Trials: An Argument for Better...

Area of Science:

• Pediatric Oncology
• Clinical Trial Design
• Drug Efficacy Evaluation

Background:

• Phase I trials traditionally focus on safety and dosing, deferring formal efficacy analysis to Phase II.
• Objective response rate (OR%) is a key metric for evaluating anti-cancer drug efficacy.
• Predictive value of early-phase trial data for later-phase outcomes is crucial for efficient drug development.

Purpose of the Study:

• To investigate the relationship between objective response rates (OR%) in paired Phase I and Phase II pediatric oncology trials.
• To determine if Phase I OR% can serve as a predictor for Phase II trial outcomes and inform study design.

Main Methods:

• A retrospective review of paired single-agent Phase I and Phase II pediatric oncology trials.
• Inclusion criteria required comparable study drug, dosing schedule, and patient population.
• Objective response rates (OR%) were tabulated, and Phase II authors' conclusions on efficacy were documented for 35 trial pairs.

Main Results:

• A strong positive correlation (0.93) was observed between Phase I and Phase II OR% in pediatric oncology trials.
• Phase II studies with positive efficacy conclusions showed significantly higher mean Phase I OR% (32.0%) compared to those with negative conclusions (4.5%).
• Phase II trials initiated despite a 0% OR% in Phase I rarely showed positive outcomes or exceeded 15% OR%.

Conclusions:

• Objective response rates in Phase I pediatric oncology trials are highly correlated with those in subsequent Phase II trials.
• Phase I OR% can provide a valuable estimate of potential Phase II response, aiding in informed decision-making for trial progression.
• Greater consideration of Phase I OR% is warranted to optimize pediatric oncology drug development and trial design.