Researchers at the University of Tsukuba have investigated the changes in the primary evaluation items in phase II clinical trials for glioblastoma, a type of brain tumor. Recently, the items have become more diverse, with more time-to-event indicators such as survival time being used, whereas the use of response rate, which indicates the proportion of patients whose cancer has shrunk, has decreased. These changes indicate that the design of trials is becoming more comprehensive and more adapted to clinical practice.

Clinical trials are conducted primarily to confirm the efficacy and safety of drugs. In the case of early-stage clinical trials for cancer, the response rate (ORR) based on the response criteria for solid tumors is typically used as the standard efficacy endpoint. However, for glioblastoma (GBM), a high-grade brain tumor, a different measure has been used because of its unique biological characteristics, such as its ability to spread into the surrounding brain tissue, often making evaluation using solid tumor efficacy criteria inappropriate.

In a study appearing in the journal Cancers, researchers analyzed the trends in efficacy endpoints established in GBM phase II clinical trials conducted worldwide in FY 2020–2022 and compared them with historical data (FY 2017–2019). Findings revealed that 101 primary endpoints (PEs) were set in 88 trials in FY2020–2022, indicating that more time-to-event measures of cancer progression control and patient survival are being used than ever before.

In particular, the progression-free survival (PFS) of 22% of subjects, the overall survival (OS) of 20% of subjects, and the PFS rate of 17% of subjects were the most commonly selected PEs used in the trials. In contrast, ORR was used as PE in only 8% of trials, indicating a significant decrease compared to 20% in FY 2017-2019. This data reveals a trend toward shifting the efficacy endpoint setting from ORR to PFS and OS. The researchers also confirmed a diversification in the types of PEs across trials and a shift toward trial designs that combine multiple endpoints rather than being biased toward specific endpoints.

These trends identified in this study reflect the complexity of GBM treatment evaluation and may indicate that clinical trial design is evolving toward more comprehensive and real-world clinical practice.

The findings from this study may guide clinical trial design, providing an essential step toward overcoming the challenges in evaluating GBM treatment and establishing more clinically relevant metrics.