Radioligand Therapy 177Lu-PSMA-617 in Progressive PSMA-positive mCRPC - Episode 1

Standard of Care for PSMA-Positive mCRPC

Andrew J. Armstrong, MD, MSc, provides insight on unmet needs and the use of androgen receptor inhibitors for patients with progressive PSMA-positive metastatic castration-resistant prostate cancer.

Andrew J. Armstrong, MD, MSc: When we talk about unmet needs in the field of advanced prostate cancer, most patients are, nowadays, offered a very potent androgen receptor [AR] inhibitor as one of their front lines of defense, either in the hormone-sensitive or non-metastatic castration-resistant setting, or in the first-line mCRPC [metastatic castration-resistant prostate cancer] setting. These patients have an improved survival rate with these potent AR inhibitors, such as abiraterone, enzalutamide, darolutamide, and apalutamide. However, over either months or years, patients will inevitably progress, despite this very potent hormonal therapy, and face this daunting prospect of chemotherapy. They will have to take docetaxel, cabazitaxel, or bone-targeting radiotherapeutics, such as radium 223. Most of these patients, when you do a PSMA [Prostate-specific membrane antigen] PET [positron emission tomography] scan, will have positive disease. About 87% of patients, for example, in the VISION study that we will be talking about, had positive PSMA PET scans that qualified them for the PSMA lutetium study. That means most patients are PSMA-positive. The unmet needs of these patients are really the unmet needs of almost all of our patients. We need to have a therapy that improves their survival, maintains good quality of life, and can put tumors into remission—ideally durably—without undue toxicities.

Precision medicine is really something that is taking the field of prostate cancer by storm. Just last year, for example, we had our first precision medicine therapies approved by the FDA [Food and Drug Administration] for patients with mCRPC, who had DNA [deoxyribonucleic acid]-homologous repair deficiencies. These were olaparib and rucaparib, for example. Again, most of these patients will also be PSMA-positive. This is illustrating the fact that these PARP [Poly (ADP-ribose) polymerase inhibitors] can improve survival in a selected, precise subgroup of patients that have DNA repair defects, particularly men with BRCA2 deficiencies. This further demonstrates the value of precision medicine in doing genetic—both germline and somatic—sequencing. PSMA is another form of precision medicine, where PSMA is a target that is expressed at the protein level and at the cell surface of the vast majority of men with prostate cancer. Unlike DNA repair defects, PSMA expression is much more broadly expressed in a cohort of men with advanced prostate cancer. Again, more than 75% of patients will have very bright PSMA expression. This is not something that can be detected with a foundation or a liquid biopsy test at this point, but rather is measured based on image or tumor expression of this marker, by protein criteria. A PSMA PET scan is 1 method to detect PSMA expression, which is the target of our PSMA-directed therapies, such as PSMA lutetium.

Transcript edited for clarity.