Characteristics and trends of globally registered glioma clinical trials in the past 16 years

Abstract

Background: Advancement in the treatment of glioma has been vacant since temozolomide has proved its therapeutic value in glioblastoma in 2005.

Aim: To help investigators understand the landscape of glioma clinical research, we analyzed the characteristics and trends of globally registered glioma trials in the past decades.

Methods: This is a cross-sectional analysis of glioma trials registered on ClinicalTrials.gov between January 2006 and December 2021. Characteristics regarding phase, enrollment number, study design and type, funding source, tumor site, pathology, patient status, age of population, trial purpose, and participating country were abstracted, and chronological shifts were analyzed.

Results: There were 1531 registered glioma trials involved 58 participating countries. The trial purpose concerning surgery, radiotherapy, chemotherapy, targeted therapy, tumor-treating fields, immunotherapy, other antiglioma therapy and non-antiglioma research trial accounts for 3.5%, 6.5%, 9.5%, 28.9%, 2.0%, 16.4%, 12.5%, and 20.6%, respectively. In the past 16 years, the numbers of chemotherapy and targeted therapy trials declined; tumor-treating fields and immune checkpoint inhibitor application trials sprang at the latter half period; Immunotherapy, other antiglioma therapy and non-antiglioma research trials escalated (all above p _trend < 0.005). The trend also showed the phased trials registered diminishingly and that the trials which focused on glioblastoma registered incrementally (those two p _trend < 0.05). Among 784 drug therapy trials, it was included 45 cytotoxic drugs, 186 targeted drugs, 19 immune checkpoint inhibitors, 78 other drugs, and five immunomodulatory drugs. Two trials belonged to Bayesian adaptive randomized design. By the end of December 2021, 309 trials had publications. Only everolimus and tumor-treating fields exhibited meaningful survival benefit in specific glioma patients in phase 3 trials.

Conclusion: Meaningful effective treatments regarding drugs or methods for glioma were difficult to be found. Bayesian adaptive platform trials may accelerate clinical research in glioma. Development of novel treatment modalities for glioma is still challenged.

Keywords: characteristics; clinical trials; glioma; landscape analysis; trends.

Figure 1.

The landscape of glioma trials in the past 16 years. The size of the bubble correlated to the counts of trials. The end date of registered trial start year was December 31, 2021.

Figure 2.

The trends of glioma trials. (a) Trend of trial phase in three groups. The first group was phase 0 to 2|3. The second group was phase 3 to 4. The third group was not applicable (NA) to phase. p_trend were <0.001, 0.023 and <0.001, respectively. (b) Trends of trials in enrolled pathological subtype of gliomas. p_trend for glioblastoma, astrocytoma, oligodendroglioma, oligoastrocytoma, and gliosarcoma were <0.001, 0.002, 0.009, <0.001, and <0.001, respectively. (c) Trends of trial purpose for surgery, radiotherapy, chemotherapy, and targeted therapy. p_trend were 0.022, 0.289, <0.001, and <0.001, respectively. (d) Trends of trial purpose for T-cell-targeted immunomodulatory, TTF, immunotherapy, other antiglioma therapy, and non-antiglioma research. p_trend were <0.001, 0.004, <0.001, <0.001, and <0.001, respectively.

Figure 3.

The landscape analysis of drugs involved in glioma trials. (a) The targeted drugs involved in glioma trials. (b) The immune checkpoint inhibitors involved in glioma trials. (c) The targeted molecules involved in glioma trials. (d) The other drugs (noncytotoxic drug) involved in glioma trials. The size of the bubble was correlated with the number of trials. Because of the crowed space, some names were not shown. The name and trial counts of every drug or targeted molecule can be reviewed in Supplemental Table S1.

Figure 4.

The numbers of trial publications every 2 years at period between 2006 and 2021. The end date of registered trial start year was December 31, 2021.