Targeted radiotherapy offers new treatment option for castration-resistant prostate cancer

The investigational therapy 177Lu-PSMA-617 significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) when added to standard of care treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) compared with standard of care alone, according to new research presented at the 2021 ASCO Annual Meeting.

“This novel targeted radiotherapy could fill a significant need for patients with metastatic castration-resistant prostate cancer that has progressed despite chemotherapy and targeted antiandrogen therapy. The success of this treatment highlights the importance of investigating alternatives to traditional types of cancer therapies,” said ASCO President Dr Lori J Pierce.

Despite recent therapeutic advances, mCRPC remains incurable. Current treatment options include chemotherapy, androgen receptor blockers, and targeted therapies. Prostate-specific membrane antigen (PSMA) is highly expressed in approximately 80 per cent of patients with prostate cancer, including in metastatic disease. With that high expression, PSMA is an attractive therapeutic target, the researchers explain.

Lutetium-labelled PSMA-617 (177Lu PSMA-617) is a radioactive compound that binds to prostate cancer cells expressing PSMA, enabling targeted delivery of radiation to the tumour and surrounding microenvironment.
The VISION trial is a phase 3 international, open-label trial of 177Lu-PSMA-617 for the treatment of mCRPC that expresses PSMA. All patients were previously treated with androgen receptor pathway inhibitors and one-to-two taxane chemotherapy regimens.

A total of 831 patients were randomised 2:1 to receive 177Lu-PSMA-617 plus standard of care, or standard of care only. The primary endpoints were PFS determined by radiography and OS. The addition of 177Lu-PSMA-617 to standard of care significantly improved radiographic PFS, compared with standard of care alone, with a median of 8.7 months, compared with 3.4 months, respectively. OS was also significantly improved, with the median 15.3 months versus 11.3 months.

More high-grade treatment-emergent adverse events were seen with 177Lu-PSMA-617, 52.7 per cent, versus standard of care, 38.0 per cent. There were no unexpected or concerning safety signals.

“The findings suggest that 177Lu-PSMA-617 warrants consideration as a new standard of care in this patient population, pending regulatory review and approval,” said lead author Dr Michael J Morris, Head of the Prostate Cancer Section at Sloan Kettering Cancer Centre, New York.