With the potential of radiopharmaceuticals as life-prolonging treatments in mCRPC, further research was driven to develop the evolving radioisotopes of today that are specifically capable of selected targeting of malignant tissues. More recently, 177Lu-PSMA-617, which delivers a beta-emitting radioisotope to PSMA targeted prostate cancer cells, has shown the most promise in improving outcomes in patients. Level I data generated from the phase 3 trial VISION demonstrated improved outcomes in patients previously treated with taxane-based chemotherapy and androgen receptor pathway inhibitors (ARPIs) and more recently for those not previously exposed to taxane-based chemotherapy in the PSMAfore trial. Other PSMA-based therapies such as 177Lu-PNT2002 have also shown activity in patients with mCRPC following progression on ARPI in the SPLASH trial.
With the promise of PSMA-based radionuclide therapy, further work into exploring novel targets, vectors, alpha-emitting radionuclide therapy, and combination therapies has expanded into new disease settings. Many studies examining the use of 177Lu-PSMA-617 in metastatic hormone sensitive prostate cancer (mHSPC), alpha therapy with actinium-225, combination therapies with tandem alpha- and beta-emitting therapies and PARP inhibitors, and novel targets such as KLK2 and STEAP1 are currently underway. As existing and novel radionuclide therapies are refined and discovered, radiopharmaceuticals may prove to be a promising treatment option for prostate cancer patients.
Written by: Jeffrey Zhong,1 & Pedro Barata, MD,2
- Case Western Reserve University School of Medicine, Cleveland, OH, United States.
- University Hospitals Seidman Cancer Center, Cleveland, OH, United States.