Dr. Ravi on Ongoing Investigation of PSMA-targeted Therapies in mCRPC

Praful K. Ravi, MB, BChir, MRCP, medical oncologist, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, instructor in medicine, Harvard Medical School, discusses ongoing and future clinical trials investigating the use of prostate-specific membrane antigen (PSMA)-targeted therapies in metastatic castration-resistant prostate cancer (mCRPC).

The targeted radioligand Lutetium 177 (¹⁷⁷Lu) PSMA-617 (¹⁷⁷Lu-PSMA-617) was previously studied in the phase 3 VISION trial (NCT03511664), Ravi begins. The trial evaluated PSMA-positive patients who were previously treated with at least one androgen receptor (AR) inhibitor and 1 or 2 taxane regimens. Results from the trial demonstrated that ¹⁷⁷Lu-PSMA-617 prolonged both median radiographic progression-free survival (rPFS) and overall survival when added to standard-of-care (SOC) treatment options in mCRPC.

There are 2 main trials currently evaluating the use of this agent in earlier stages of mCRPC, Ravi continues. The phase 3 PSMAfore trial (NCT04689828) is comparing the effect of ¹⁷⁷Lu-PSMA-617 vs changing AR-directed therapy (ARDT), on the risk of radiographic progression or death, he explains. The trial population consists of patients with mCRPC or metastatic hormone-sensitive prostate cancer (mHSPC) who were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen. A recent press release stated that the trial had met its primary end point of a clinically meaningful improvement in rPFS, but initial data are still forthcoming, Ravi notes.

Additionally, the phase 3 PSMAddition trial (NCT04720157) aims to investigate the efficacy and safety of ¹⁷⁷Lu-PSMA-617 in combination with SOC androgen deprivation therapy (ADT) plus ARDT compared with ARDT and ADT alone in patients with mHSPC, Ravi says.

Aside from these large-scale efforts, several smaller trials have been designed to investigate ¹⁷⁷Lu-PSMA-617 in combination with PARP inhibitors or immunotherapies, Ravi says. Future research will likely continue the development of these novel combination regimens and focus on implementing PSMA-targeted strategies in earlier stages of disease, he concludes.