EPID-07. A SYSTEMIC REVIEW OF PHASE II SINGLE-ARM TWO-STAGE DESIGNS IN GLIOBLASTOMA

Abstract

Abstract Even though two-stage designs have been popularly in oncology Phase 2 single-arm trials during last decade, none, to our knowledge, has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in glioblastoma. It might be valuable to perform a comprehensive review on the phase 2 single-arm two-stage trials in glioblastoma for examination of appropriate application on the two-stage designs. Systematic review has been performed under the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-statement. The search was performed using following key words for the literature search as index terms or free-text words: “phase II trials”, “glioblastoma”, and “two-stage design”. After identifying 81 articles based on online search, we had 32 studies included in review due to exclusion of 49 articles such as duplicates (n = 10), randomized trials (n = 7), single-stage designs (n = 5), and insufficient information (n = 27). We extracted general and two-stage design information (tumor type and setting, drugs, error types, response rates, primary endpoint, two-stage sample size data, study termination status etc). Almost 50% of single-arm two-stage studies failed to provide key information related to study designs and sample size calculation, even wrong power analysis and interpretation. Response rate and progression-free survival are used as popular surrogate endpoints for overall survival. It is time to evaluate other potential endpoints like post-progress survival and hazard ratio, and usefulness of co-primary endpoint. Studies less than 10% provided the historical data source. Investigators should keep transparency of the trials by fully providing and citing historical data source and do conservative choice for historical rates. Meta-analysis can be a good option to accurately estimate the historical control. The appropriate selection on primary endpoint, historical control data, incorporation of adaptive designs, right application of two-stage designs might help overcoming the challenges on glioblastoma therapeutic trials.