Henrik Grönberg, MD, PhD, Karolinska Institute, Stockholm, Sweden, shares insights from the phase 3 ProBio trial. This trial uses the innovative “outcome-adaptive” trial protocol to compare androgen receptor pathway inhibitors with taxanes for metastatic castration-resistant prostate cancer.

The results found that progression-free survival and overall survival were improved with androgen receptor pathway inhibitors, compared with both standard of care and taxanes in this patient population. Additionally, Dr Grönberg noted, “We can use innovative trial designs like ProBio with outcome-adaptive randomization based on biomarkers in oncology today."

Dr Grönberg shared these results at the 2023 ESMO Annual Congress.

Transcript:

Hi, my name is Henrik Gronberg. I'm a medical oncologist from Karolinska Institutet in Stockholm, Sweden, and I'm here at ESMO 2023 in Madrid. Today I presented a study which is called ProBio, Prostate Biomarkers, and it's a study of men with metastatic prostate cancer. One of the problems we are facing when we are treating patients with metastatic prostate cancer is that we have many different drugs and we don't know which one to choose first from the other. We have started a large investigator/academic-run randomized trial where we use biomarkers, circulating tumor DNA to randomize patients to different experimental arms and compare that to standard of care. This study is run in 4 European countries Sweden, Norway, Belgium, and Switzerland.

The ProBio is a very innovative oncology trial. It's actually the first time that we use what we call outcome-adaptive randomization. And what does that mean? Well, that means that we change randomization probabilities over time during the study period based on the results from each patient. So for example, if I have a patient that have a specific biomarker signature that is given a specific drug and he responds, the next time a similar patient comes in to this study, it increases the chance that he will get that study drug. And vice versa. If the drug doesn't work in this specific first patient, the chances decreases. So it's outcome-adaptive. And this is actually the first time it's been used in oncology.

Today, I presented the first results where we compared standard of care, physician choice of a treatment, in men with castration-resistant prostate cancer and compared that to patients that received androgen receptor pathway inhibitors, or taxanes. The results showed that androgen receptor pathway inhibitors were superior, both when it comes to progression-free survival and overall survival, compared to both physician's choice and to taxanes. And the interesting thing, if you look at overall survival, the men that received the androgen receptor inhibitors, which in this case was abiraterone or enzalutamide, they lived for about 38 months compared to 22 months in the other 2 groups, taxanes or physician choice.

And I think the key take home message from this study is that if a patient have received an androgen receptor inhibitor before in the treatment of metastatic prostate cancer, he should get that before he will get taxanes. The other thing that we also see in different biomarker signatures is that for 2 of the biomarker signatures, this was true for those with no mutation in the androgen receptor or the p53 gene or fusion gene TMPRSS2-ERG, those benefited from androgen receptor inhibitors. However, those with p53 mutations, there was no difference between taxanes and androgen receptor inhibitors and physicians choice.

And I think except for the main results, I think one thing that we show today is that we can use innovative trial designs like ProBio with outcome adaptive randomizations based on biomarkers in oncology today.

Source:

Grönberg H, Lindberg J, De Laere B, et al. Adrogen receptor pathway inhibitors or taxanes for patients with metastatic castration-resistant prostate cancer: A direct comparison in ProBio, a randomized outcome-adaptive, biomarker-drive platform trial.