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Spotlight

This roundtable series evaluates radioligand therapy in patients with previously treated metastatic castration-resistant prostate cancer with positive prostate-specific membrane antigen, as discussed by participants at virtual live events.

Later-Line Options for Patients With PSMA-Positive mCRPC

Daniel J. George, MD, professor of medicine, medical oncology, and surgery at Duke Cancer Institute, discusses why he considers using prostate-specific membrane antigen (PSMA) imaging early in treatment of patients with castration-resistant prostate cancer (CRPC).

A PSMA PET scan can detect distant metastases of prostate cancer early and is required before treating patients with the radioligand 

Lutetium-PSMA-617 (Pluvicto), which showed strong efficacy in the VISION trial (NCT03511664).

George says now that PSMA-targeted therapy is available, he considers PSMA imaging before patients receive chemotherapy for CRPC. Knowing whether he can give 

Lutetium-PSMA-617 next will inform his decision to continue chemotherapy if patients have difficulty tolerating it.

Otherwise, he recommends a PSMA PET scan after chemotherapy so patients can receive radioligand therapy if necessary, though he may not do imaging immediately if patients have a positive response to therapy with no rise in prostate-specific antigen (PSA) or other signs of clinical progression. When there is a rise in PSA after prior therapy, he recommends starting the process to receive 

Lutetium-PSMA-617 since it can take time for insurance to approve treatment.

 When I'm thinking about the castration-resistant population, patients who might be good candidates for radioligand therapy or particular for Pluvicto therapy, PSMA-targeted therapy, I want to think about doing my imaging in those patients a little bit earlier. I actually like to do that imaging before they go on to chemotherapy, because then I know this is going to be someone who I'm going to sequence, and it affects how I use my chemotherapy. I may not push that chemotherapy to the very last cycle, cycle 10 or cycle 9 if they're struggling; I'll stop a little bit early because I know I have this other therapy to follow. Or, if their PSA response seems to have really flattened out and it's not clear how much additional benefit they're getting, I'll stop a little bit earlier. I like to do my PSMA imaging before, now. Of course, this is an evolving time. We didn't have that available 6 months ago, so it's a little kind of in the future here.

But the other time is when to do the imaging right after chemotherapy. Sometimes those patients, if they've responded, may not have the best images. So if I have a patient that's on docetaxel chemotherapy or cabazitaxel, and they've had a really good response to therapy and I'm taking a treatment break, I'm not going to immediately image them until I start to see that PSA rise or some other clinical signs of progression. Then I'm going to do my PSA imaging and then I'm going to think about treatment with Pluvicto.

Daniel J. George, MD, discusses why he considers using prostate-specific membrane antigen imaging early in treatment of patients with castration-resistant prostate cancer.

Expert Discusses When to Perform PSMA PET Imaging for Metastatic CRPC

Michael J. Morris, MD, prostate cancer section head for genitourinary oncology at Memorial Sloan Kettering Cancer Center, discusses the results of the VISION trial (NCT03511664) of 

lutetium-PSMA-617 (Pluvicto) in patients with metastatic castration-resistant prostate cancer (mCRPC).

The phase 3 VISION trial randomly assigned patients with mCRPC who were prostate-specific membrane antigen (PSMA)-positive 2:1 to receive best supportive care/standard-of-care therapy with or without 

lutetium-PSMA-617 once every 6 weeks for 6 cycles. Patients had previously been treated with 1 or 2 taxane-based regimens and androgen-receptor targeted therapy. The primary end points were radiographic progression-free survival (rPFS) and overall survival (OS).

lutetium-PSMA-617 had a 38% improvement in OS, with a median OS of 15.3 months versus 11.3 months with standard of care. Their rPFS was improved by 60%, with a median of 8.7 months with 

lutetium-PSMA-617 versus 3.4 months with standard of care. A secondary end point, time to first symptomatic skeletal event (SSE) was 11.5 months versus 6.8 months, respectively.

In terms of toxicity, there was an increase in high-grade adverse events for 

lutetium-PSMA-617, including grade 3 and 4 hematologic toxicity in 10% of patients. Other AEs included gastrointestinal (GI) toxicity and dry mouth. Overall, Morris says this therapy offers favorable efficacy and acceptable toxicity in this patient population.

 VISION was a phase 3 randomized study which took patients whom I just described, that is those who had progressed through androgen receptor signaling inhibitor and who had progressed through chemotherapy. These patients were PSMA-avid on a gallium-68 PSMA 11 scan. The design of the trial was patients before randomization were given a protocol defined as standard of care by their treating physician and then randomized to either receive Pluvicto or not.

Those who received Pluvicto had about 40% improvement in OS, about a 60% improvement in terms of rPFS, a 50% improvement in the likelihood of remaining free of a SSE. And in terms of toxicity, a modest amount of grade 3 and 4 hematologic toxicity, around 10%. [There was] some mild GI toxicity, around 40% of patients, [and] xerostomia in around 40% of the patients, also mild. So relatively, for this advanced patient population, a relatively favorable trade-off in terms of risk versus benefit in favor of treatment.

Michael J. Morris, MD, discusses the results of the VISION trial of 177-lutetium-PSMA-61 in patients with metastatic castration-resistant prostate cancer. 

Targeted Radioligand Therapy Shows Efficacy in PSMA-Positive mCRPC