Measures of progression-free survival cannot be used as substitute measures for overall survival in clinical trials of malignant mesothelioma, according to an analysis of data from 17 trials.
The findings offer insight into how clinical trials should be designed by showing that, so far, there is no shortcut for measuring overall survival.
The study, “Validation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials,“ was published in the journal The Oncologist.
In trials of potential mesothelioma treatments, overall survival is the most important measure. But circumstances such as long follow-up times and the effects of later treatments can make it an impractical yardstick.
Many studies allow patients receiving a placebo to switch to the actual treatment after an initial study period. Researchers have discussed if progression-free survival is a good enough substitute for overall survival in such cases.
Researchers at Duke University in North Carolina looked at 716 patient outcomes in 17 Phase 2 clinical trials. The information came from two datasets.
Since factors other than the treatment are known to influence mesothelioma survival, the team included information about patients’ age, tissue and cell examinations, white blood cell count, and cancer risk in their analysis. The risk-score index they used was the European Organisation for Research and Treatment of Cancer (EORTC) assessment.
The patients’ median progression-free survival rate was three months, and the median overall survival rate 7.2 months. The research team detected only a weak correlation between the two measures. They saw the same result when they included only patients who had not received chemotherapy before entering a clinical trial.
When other risk factors were included one by one in the analysis, the team noted that correlations varied by risk factor. Including information about tissue and cell examinations and white blood cell count yielded a good correlation between progression-free and overall survival. But for all other factors, the correlation was minimal.
The analyses demonstrated that there is little support for using short-term progression-free survival measurements as a substitute for overall survival. That’s especially true due to the differences in the way various factors influence the relationship between the two measurements.