Using blood samples to guide cancer treatment: first lessons from unique 'ProBio' study

Prostate cancer diagnosed in an early stage has a very good prognosis. Unfortunately, this does not hold true for metastatic prostate cancer. Not all patients respond well to the existing chemotherapy and new targeted hormonal treatments, and it is difficult for the treating physician to assess which treatment has the best chance of success for a given patient. The “ProBio” (prostate biomarkers) study addresses this need in a unique way. The first results have now been published in Nature Medicine.

A unique set-up
In most clinical trials, treatments are compared side by side by dividing patients into two groups: a group receiving the new treatment and a control group treated in the standard way. However, this classical method has drawbacks: such studies are mostly designed from a “one-treatment-fits-all” point of view, patients are not selected beforehand, and the ultimate goal is to proof that the new treatment outperforms the standard treatment on average. Moreover, there is no plan B for patients in the control group, or for whom the new treatment does not (sufficiently) work. In those cases, the study stops for the patient in question, who continues to be treated in routine care. 

The ProBio study seeks to overcome these drawbacks. Patients in whom the treatment fails may receive another treatment with greater chances of success during the course of the study.  Patients may thus be assigned to a new treatment up to three times.

Precision medicine and increased patient selection
Also unique to ProBio is the use of liquid biopsies: for those eligible to enter the study, a liquid biopsy - here a blood sample - is used to determine the patient's genetic profile before assigning them to a particular study group. In this way, the study can show links between the occurrence of certain genetic changes and whether or not the patient responds to a particular type of treatment. Thus, prostate biomarkers can be identified.

First results: p53 found to be defining protein
Since the study began in 2019, 784 patients from 31 hospitals in Belgium, Sweden, Norway and Switzerland have already participated in the study. The first results in 193 patients treated with a new hormonal agent, chemotherapy, or a treatment chosen by the doctor have now been published in Nature Medicine. Across all groups, the researchers saw that patients who received new hormonal agents did better than those treated with taxane-based chemotherapy. 

When zooming in on the groups based on the blood genetic tumor profiles, the difference in outcome between new hormonal agents and chemotherapy was most pronounced in the group of patients in whom no DNA changes could be found in the genes for p53 (an important protein involved in repairing errors in DNA) and the androgen receptor (an important hormone receptor). In patients with alterations in p53, none of the treatments appeared to work well, highlighting the importance of further research into new treatments for these patients. 

ProBio as a model
The ProBio study already provided many relevant insights, and is expected to continue to do so in the coming years. Besides the individual conclusions, the study shows that it is possible to use a liquid biopsy for biomarker analysis to guide cancer treatment. ProBio can thus serve as a model for other studies, contributing to the transition to more personalized medicine in oncology. 

The ProBio study by Dr. Bram De Laere and partners from the Karolinska Institute (Sweden), together with Prof. Piet Ost (UGent), was brought to Belgium with the support of Kom Op Tegen Kanker. The international research collaboration between CRIG and the Karolinska Institute is also supported by the Ghent University International Thematic Network (ITN) on 'Precision oncology, Immuno-Oncology and Modeling in Cancer', called ‘PrIOMiC'.

You can read more about this interesting research in the Nature Medicine publication & on the website of the ProBio trial.