TAT-11: Alpha Therapeutics from a Prostate Oncologic Standpoint

Ottawa, ON, Canada (UroToday.com) Dr. Michael Morris began by describing the microenvironment around bone tumors. The tumor growth is affected by both osteoclasts and osteoblasts. It is important to realize that Radium-223 attacks this microenvironment and not the tumor itself. Nonetheless, Radium-223 has been shown in clinical trials to significantly improve overall survival (14.9 months median OS compared to 11.3 months for placebo). However, there is still an advantage to adding an agent that attacks the tumor directly (such as the chemotherapy drug like docetaxel) to Radium-223. Alternatively, there is a role for traditional targeted alpha therapy such as Ac225-PSMA to attack the tumor directly.

As an example of such combination therapy, Dr. Morris described the DORA trial, now advancing to Phase III. This study has 738 patients. In one arm patients receive docetaxel 75mg/m2 every three weeks for 10 doses plus daily doses of prednisone 5mg. The other arm adds Radium-223 55kBq/kg for 6 injections every 6 weeks. The primary endpoint is overall survival with secondary endpoints of PSA, bone markers, imaging, and quality of life.

Dr. Morris described another clinical trial for combination therapy using Radium and atezolizumab, an immunotherapy agent. The trial design begins with dose-limiting toxicity observation in three cohorts: the first with concurrent application of radium and atezolizumab, the second with staggered dosing of the agents, and the third with staggered dosing on a longer radium run-in time. If the initial therapy is tolerated, the trial progresses to a randomized treatment evaluation with three arms. The first arm is concurrent dosing, the second staggered dosing with a radium run-in, and the third staggered dosing with an atezolizumab run-in.

In looking at future directions, Dr. Morris noted the need for formal trials that address toxicity and patient risks: alternative targeting, reconsidering molecule size, and treatments for xerostomia. Finally, although targeted alpha therapy undoubtedly has great promise, we still need data supporting actual clinical benefits. As Dr. Morris put it, "enthusiasm cannot replace equipoise."