Cancer immunotherapy trial design with cure rate and delayed treatment effect.

Cancer immunotherapy trials have two special features: a delayed treatment effect and a cure rate. Both features violate the proportional hazard model assumption and ignoring either one of the two features in an immunotherapy trial design will result in substantial loss of statistical power. To properly design immunotherapy trials, we proposed a piecewise proportional hazard cure rate model to incorporate both delayed treatment effect and cure rate into the trial design consideration. A sample size formula is derived for a weighted log-rank test under a fixed alternative hypothesis. The accuracy of sample size calculation using the new formula is assessed and compared with the existing methods via simulation studies. A real immunotherapy trial is used to illustrate the study design along with practical consideration of balance between sample size and follow-up time.