Characteristics and trends of globally registered malignant pleural mesothelioma clinical trials in the past 27 years.

Abstract

e20544 Background: Malignant pleural mesothelioma (MPM), arising from the serosal lining of the thoracic cavity, is a rare malignancy with limited treatment options and very poor prognosis. Recent progress in immunotherapy and innovative devices have advanced treatment fields of MPM. To help investigators understand the landscape of MPM clinical research, characteristic and trends of globally registered trials in the past decades were analyzed in our study. Methods: This is a cross-sectional analysis of MPM trials registered on ClinicalTrials.gov between January 1996 and December 2022. Characteristics pertaining to trail phase, enrollment number, study design, type, funding source, age of population, trial purpose, and participating country were extracted, and chronological shifts were analyzed. Clinical trial variables were enumerated using descriptive statistics and categorical data were presented as frequencies and percentages. Chi-square trend analysis (Cochran–Armitage trend test) was used to evaluate the trend of MPM trials. Results: 267 registered MPM trials were analyzed involving 40 participating countries among which the United States, the United Kingdom, and Italy were top 3. 8.2% trials were phase 3 and 18.7% were randomized. 74 trials had publications by the December 2022. The trial purposes concerning surgery, radiotherapy, chemotherapy, target therapy, immunotherapy, photodynamic therapy, cryotherapy, tumor treating fields （TTF）and non-anticancer research accounted for 2.6%, 5.2%, 20.2%, 25.5%, 31.1%, 1.1%, 0.7%, 0.7% and 12.7% respectively. In the past 27 years, the numbers of chemotherapy and targeted therapy trials declined while immunotherapy trails steadily escalated (all above ptrend < 0.05). There are no significant changes for the trends of each trial phase. 205 drug therapy trials involved 26 cytotoxic drugs, 44 targeted drugs and 11 immune checkpoint inhibitors and 34 other drugs. Pemetrexed-cisplatin with TTF and ipilimumab-nivolumab have changed the frontline treatment space while improvement for regulatory approvals has been far slower in salvage treatment, with the median overall survival all less than 11 months in phase 3 trials. There are no definitive trials that justify the use of predictive biomarkers for systemic therapy in MPM. Conclusions: Immunotherapy and TTF have reshaped the standard of care landscape over the past 27 years. With the enhanced understanding of molecular characteristics and mechanism of MPM, it is anticipated that ongoing immunotherapy combined with target therapy, chemotherapy or other novel treatment can improve the frontline and post-line therapeutic effect.