Historical Controls for Metastatic Pancreatic Cancer: Benchmarks for Planning and Analyzing Single Arm Phase II Trials.

Publication Type:

Journal Article

Source:

Clinical cancer research : an official journal of the American Association for Cancer Research (2014)

Keywords:

2014, July 2014, Public Health Sciences Division

Abstract:

We compiled a database of cooperative group trials in metastatic pancreatic cancer, to develop historical benchmarks for overall survival (OS) and progression free survival (PFS). Benchmarks are essential for evaluating new therapies in a single arm setting. Patients with untreated metastatic pancreatic cancer receiving regimens that included gemcitabine, between 1995 and 2005, were included. Prognostic baseline factors were evaluated by Cox regression analysis. Outlier trial arms were identified by comparing individual 6-month survival rates against the entire group. The dataset selected for the generation of OS and PFS benchmarks was then tested for inter-trial arm variability using a logistic-normal model with selected baseline prognostic factors (sex and performance status) as fixed effects and the individual trial arm as a random effect. 1,132 cases from eight trials qualified. Outcomes for one trial (NCCTG-034A) were significantly different from the others. Excluding this trial, the remaining trial arms were homogeneous for OS and PFS outcomes after adjusting for performance status and sex. Benchmark values for 6-month OS and PFS are reported along with a method for using these values in future study design and analysis. The benchmarks can be used to enable single-arm phase II trials utilizing a Gemcitabine platform, especially under certain circumstances. Such circumstances might be when a randomized control arm is not practically feasible, an early signal of activity of an experimental agent is being explored such as in expansion cohorts of phase I studies, and in patients who are not candidates for combination cytotoxic therapy.