Dr Michiel Strijbos, a GU oncologist at GZA Wilrijk, conducts an insightful interview with Prof Henrik Grönberg from the Karolinska Institute in Stockholm, shedding light on the innovative ProBio trial, a groundbreaking trial that employs statistical methods previously untapped in the field of medical oncology.
ProBio stands out as an outcome-adaptive randomised trial, simultaneously evaluating numerous biomarkers and treatments guided by the ctDNA biomarker. One of its most pioneering features is the use of outcome-adaptive randomisation, wherein randomisation probabilities shift over time based on individual patient responses. For instance, when a specific patient receives a treatment determined by biomarkers and responds favourably, subsequent patients with similar profiles are more likely to receive the same treatment. Conversely, if the treatment is ineffective for the first patient, the likelihood of the next patient receiving that treatment diminishes. This dynamic randomisation approach significantly enhances the trial’s efficiency, obviating the need for a large sample size of a thousand patients in traditional randomised trials. It also expedites the availability of results. The trial’s inception on a small scale in Sweden roughly three years ago yielded the first graduation of an arm superior to the standard of care as early as December last year.
While the turnaround time for ctDNA analysis can be a challenge in some centers, taking 2 to 3 months for results, this issue was effectively addressed in the ProBio trial. Participating centers across Sweden, Belgium, Norway and Switzerland sent their samples to the Karolinska Institute in Stockholm, receiving reports on average within 13 days. However, it is important to note that approximately one-third of patients cannot be included in the study because ctDNA cannot be detected in their cases. Notably, patients who received one of the new androgen receptor pathway inhibitors (ARPI) exhibited a higher likelihood of having negative ctDNA results.
Another innovative facet of the trial concerns the re-randomization of patients upon disease progression, a scenario encountered by roughly one-third of patients in this analysis. Additionally, the trial’s flexibility in integrating new treatment options as they become available holds considerable promise for the future of oncology research.
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