EAU Congress: PSMA agents hailed as launching “new era of precision medicine in urology”

Researchers at the 2021 European Association of Urology (EAU) Congress hailed PSMA targeted therapies and diagnostics—jointly known as theranostics—as a revolutionary new approach to treating patients with advanced prostate cancer.^1,2

The high praise came amid the backdrop of a webcast presentation of the pivotal findings from the phase 3 VISION trial. In the study, adding the PSMA-targeted radioligand therapy 177Lu-PSMA-617 (LuPSMA) to standard of care (SOC) led to a nearly 40% reduction in the risk of death versus SOC alone in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).

The open-label VISION trial included 831 patients who received at least 1 novel androgen axis drug (eg, enzalutamide [Xtandi] or abiraterone acetate [Zytiga]) and were previously treated with 1 to 2 taxane regimens. PET imaging with 68Ga-PSMA-11 was used to determine PSMA positivity. The median overall survival (OS) was 15.3 months in the LuPSMA arm versus 11.3 months in the SOC alone arm, translating to a 38% reduction in the risk of death (HR, 0.62; P <.001).The median radiographic progression-free survival (rPFS) was 8.7 versus 3.4 months, respectively (HR, 0.40; P <.001).

"Using the PSMA molecule to directly target prostate cancer cells is the beginning of a new era of precision medicine in urology diagnostics as well as therapy", Peter Albers, MD, head of the Department of Urology, Dusseldorf University, and Chair of the Scientific Office of the EAU, stated in a press release. "LU-PSMA-617 was tested in so-called end-stage disease and still showed superiority and this paves the way for studies to treat patients in earlier stages. We have seen similar success in the diagnostic setting, using this molecule to improve the way we stage tumors. This targeted approach will revolutionize the way we approach the treatment of men with prostate cancer in the future."

In the VISION study, patients were randomized in a 2:1 ratio to LuPSMA (7.4 GBq every 6 weeks x 6 cycles; n = 551) plus SOC or SOC alone (n = 280). Individual investigators determined the SOC; however, radium-223 (Xofigo) and cytotoxic chemotherapy were not allowed. The coprimary end points of the trial were OS and rPFS.

Beyond the OS and rPFS benefits, there was also a statistically significant benefit favoring the LuPSMA arm for the key secondary endpoints of objective response rate (ORR), disease control rate (DCR), and time to first symptomatic skeletal event (SSE). The ORRs and DCRs were 29.8% versus 1.7% and 89.0% versus 66.7%, respectively. The median time to first SSE was 11.5 months in the LuPSMA group compared with 6.8 months in the control arm (HR, 0.50).

"Our findings show that this potent radioactive medicine can deliver radiation precisely to cancer cells and destroy them, extending patients' lives. I hope men whose tumors have high levels of PSMA can soon benefit from this highly innovative treatment,” lead study author Johann de Bono, MD, professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, stated in the press release.

Study investigator Ken Herrmann, MD, director of the Clinic for Nuclear Medicine at University Hospital Essen, Germany, added in the release, “This is a completely new therapeutic concept; a precision medicine that delivers radiation directly to a high incidence tumor. The treatment was well tolerated by patients and they had an average of four months' longer survival with good quality of life. Lu-PSMA-617 can improve the lives of many men with advanced prostate cancer and their families.”

References

1. De Bono. Phase 3 study of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). Presented at 36th Annual EAU Congress (virtual). July 8-12, 2021.

2. New concept drug hunts down late-stage prostate cancer. Published online July 10, 2021. Accessed July 13, 2021. https://bit.ly/3knbyOu.