Dr Smith on the Role of Radioligand Therapy in Prostate Cancer

“Radioligand therapy is here to stay in prostate cancer. [There have been] a lot of new data, and the flow of data will continue.”

Matthew R. Smith, MD, PhD, the Claire and John Bertucci Endowed Chair in Genitourinary Cancers and the director of the Genitourinary Malignancies Program at Massachusetts General Hospital, as well as a professor of medicine at Harvard Medical School, discussed the evolving role of radioligand therapies for the treatment of patients with prostate cancer.

Smith noted that radioligand therapy has made a significant splash in prostate cancer management in recent years and that the approach is likely here to stay. Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is an effective treatment option for patients with prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer (mCRPC) following the FDA’s decision in March 2025 to expand the indication of the agent to include patients who have been previously treated with androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy. The approval was supported by data from the phase 3 PSMAfore trial (NCT04689828), which showed that patients who received lutetium Lu 177 vipivotide tetraxetan experienced a significant radiographic progression-free survival benefit compared with those who switched to another ARPI (HR, 0.41; 95% CI, 0.29-0.56; P < .0001). The median rPFS was 9.3 months (95% CI, 7-not estimable) with the investigational combination vs 5.6 months (95% CI, 4-6) with switch to another ARPI. Additional data from the trial are anticipated, including updated overall survival findings, Smith said.

Moreover, findings from the phase 3 PEACE-3 trial (NCT02194842) showed a benefit with the addition of radium-223 dichloride (Xofigo) to enzalutamide (Xtandi) in terms of rPFS vs enzalutamide monotherapy (HR 0.69, 95% CI, 0.54-0.87; P = .0009) for the treatment of patients with mCRPC, Smith said. These findings were somewhat unexpected and have led investigators to revisit the role of radium-223 in this patient population, he concluded.