Dr. Park on the ARASENS and TITAN trials in mHSPC

Chandler Park, MD, MSc, FACP, co-director, Genitourinary Clinical Trials at Norton Cancer Institute in Louisville, Kentucky, discusses lessons for clinical practice learned from the ARASENS and TITAN trials in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Transcript

The ARASENS trial compared docetaxel/ADT, which is considered a standard of care, versus the androgen pathway inhibitor darolutamide (Nubeqa) plus docetaxel/ADT. This phase 3 study randomly assigned 1300 patients with mHSPC across the world. And what they found in this study was the triplet therapy showed a survival benefit over docetaxel/ADT alone. So therefore, this triplet is considered one of the standard of cares for newly diagnosed mHSPC. There is one caveat though and that is Dr. Neeraj Agarwal, one of the leaders in prostate cancer, showed that in the TITAN study, which evaluated apalutamide (Erleada) plus ADT in mHSPC, there was also survival benefit in high volume and low volume patients.

Based on the CHAARTED study, high volume patients are considered patients with mHSPC with 4 or more bone lesions with 1 of the lesions outside of the actual skeleton. So for instance, if you had a cancer in the femur or the humerus that's considered a high volume based upon the number of bones as long as 1 of the 4 bones is outside of the exoskeleton or if you had metastatic disease in the liver or lung. And so what Dr. Agarwal and his colleagues have shown in the in the TITAN study is that there was a survival benefit for high volume and low volume.

And so that brought all the people together in the prostate community and said, perhaps the standard of care arm for the ARASENS study should have been the androgen pathway inhibitor with ADT. Unfortunately, that is not the comparison arm. And so, how do we determine which patients get the triplet therapy with darolutamide and docetaxel/ADT versus an androgen pathway inhibitor and ADT? And the answer is, this is a very controversial topic. But for patients with high risk, high volume disease—high risk is considered patients with either metastases in the liver or the lung with the high volume that I mentioned, if they also have somatic gene mutations known as TP53, PTEN, and RB1, these somatic mutations in prostate cancer portend a very aggressive cancer, and therefore, these patients should be treated very aggressively. On the other hand, for the patients that are considered low volume disease, even though the triplet therapy is very effective, we should consider just doing an androgen pathway inhibitor, whether it be apalutamide with ADT or enzalutamide (Xtandi) with ADT.

This transcript has been edited for clarity