Dr George on the Role of Radioligand Therapy in Prostate Cancer Management

“Lutetium Lu 177 vipivotide tetraxetan has shown us is that there is a role for this therapy throughout the disease continuum, from hormone-sensitive disease all the way through chemotherapy-refractory castration-resistant disease.”

Daniel J. George, MD, the Eleanor Easley Distinguished Professor in the School of Medicine, a professor of medicine, a professor in urology, and a professor in surgery in the Department of Medicine at the Duke University School of Medicine; as well as a member of the Duke Cancer Institute, discussed the therapeutic potential of radioligand therapies for patients with prostate cancer and the subsequent evolution of clinical trial goalposts within this treatment paradigm.

The radioligand therapy Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) has had a crucial role in prostate cancer management, spanning from the management of hormone-sensitive disease all the way through to the treatment of chemotherapy-refractory castration-resistant disease, George began. As Lutetium Lu 177 vipivotide tetraxetan moves into earlier and earlier disease settings—a pattern similar to the historical development and deployment of androgen receptor pathway inhibitors—the established goals for clinical success have necessarily changed, he noted. There is now less concern about overall survival (OS) end points when moving into earlier disease settings, largely because the outcomes for these patient populations are influenced by other confounding factors, he explained.

Instead of prioritizing OS or radiographic progression-free survival outcomes, which have historically been the traditional metrics used in registrational trials for patients with early metastatic hormone-sensitive prostate cancer, George expressed greater enthusiasm for the capability of radioligand therapy to achieve minimal residual disease (MRD). Individual patient treatment goals are not always reflected in the historical trial metrics, he said. However, patients often desire to successfully achieve MRD so they can discontinue therapy, he reported.

Moving forward, if radioligand therapies become a standard component across more areas of the prostate cancer treatment paradigm, they may be used in various sequences, according to George. These potential strategies include fist-line combinations, or induction therapy that is followed by either consolidation or maintenance therapy, he continued. Through these integrations, it is possible that radioligand therapies could enable certain patients in the metastatic hormone-sensitive setting to successfully discontinue treatment, he added.

The overarching objective is to identify and employ a specific combination or sequence of therapies that maximizes the number of patients who reach MRD and are ultimately able to cease treatment, George stated. Although achieving a cure remains the ultimate aspiration, a welcome result for patients is even a break from therapy, which helps to restore their overall health and functionality, he concluded.