Radioligand Therapy 177Lu-PSMA-617 in Progressive PSMA-positive mCRPC - Episode 4

Patient Selection of LuPSMA Therapy in mCRPC

An expert in prostate cancer comments on the appropriate patient population for Lutetium-177 PSMA-617 therapy for the management of metastatic castration-resistant prostate cancer.

Andrew J. Armstrong, MD, MSc: A great question is which patients are most appropriate for Luetetium-177 PSMA (Prostate-specific membrane antigen)-617? The FDA [Food and Drug Administration] has yet to approve this PSA [prostate-specific antigen]-based therapy yet. We do not know for sure what the FDA label will have. For example, in the VISION trial, all patients were required to have a PSMA PET [positron emission tomography] scan, demonstrate PSMA positivity, and a lack of disease that was PSMA-negative. I would expect 1 possible indication for this therapy would be very similar to the VISION type patient: a patient with metastatic castration resistance, who has progressed, despite a potent AR [androgen receptor] inhibitor and docetaxel. Another possible patient would be unfit for docetaxel and have positive PSMA disease on a PSMA PET scan. One could argue that this was such a broadly effective therapy, and that so many patients are positive for PSMA anyway—nearly 85%—that this may be effective, even without the need for a PSMA PET, which would increase barriers to access, and add cost to this therapy. Since it is such a broadly effective agent, it remains to be determined whether the PSMA PET will be required. The patients, in my experience, who tend to have PSMA-negative disease, which you need to watch out for—because this may not be an appropriate therapy for such patients—would be those with small cell or neuroendocrine prostate cancer. These patients are known to lack PSMA. This would not be an appropriate PSMA-targeting strategy for these patients. They are likely not to respond. These such patients are more likely to have liver or visceral metastases. While some patients with visceral metastases can have PSMA, most patients with liver metastases have very scattered or low PSMA expression. This would be a word of caution for these patients. If you know that a patient has small cell or neuroendocrine differentiation, it would be more appropriate to consider alternatives to this approach.

The impact of this for our patients, once the FDA has approved this, would be that this adds another life-prolonging therapy to the armamentarium of what we have already. The life-prolonging therapies that we have available to us in the mCRPC [metastatic castration-resistant prostate cancer] setting are abiraterone, enzalutamide, and sipuleucel-t. We use olaparib for DNA [deoxyribonucleic acid] repair-deficient patients and radium for patients with bone metastases that are symptomatic. We use docetaxel and cabazitaxel more broadly.

Then, PSMA lutetium would be for patients who have failed with an AR inhibitor and a taxane. The question will be, where do you fit this in? Some studies have compared, in small phase 2 trials, PSMA lutetium against cabazitaxel. And PSMA lutetium performs comparably to cabazitaxel, with improved PSA outcomes, better quality of life, and improved tolerability. There are many patients in our clinics that are not candidates for further chemotherapy, or have exhausted their chemotherapy outcomes, because of side effects, comorbidities, and age. They prefer not to get more chemotherapy. This represents a very good therapy regarding quality of life. The toxicities of PSMA lutetium do include some bone marrow toxicities, such as platelet counts, some dry mouth, dry eyes, and fatigue, due to the marrow suppression, but not to the degree that typically cabazitaxel or docetaxel produces. There are no impacts, generally, on infection risk. There is no hair loss. There is not the typical side effects of chemotherapy that most men are accustomed to experiencing.

Transcript edited for clarity.