Shared insight on the VISION trial, which analyzed 177 Lu-PSMA-617 in previously treated PSMA-positive metastatic castration-resistant prostate cancer.
Alan Bryce, MD: Lutetium is based on the phase 3 VISION study. Everybody has heard of this by now. It was a slightly complicated study design. I’ll try to walk through it step by step. The patients were required to have at least 1 next-generation androgen receptor pathway inhibitor and at least 1 line of taxane chemotherapy. This was a randomized study vs protocol-permitted standard of care. The control arm was not an absence of therapy, and even the treatment arm was lutetium plus that same standard of care. Based on the exclusions, that meant either abiraterone or enzalutamide, 1 of the oral androgen pathway inhibitors. Patients were required to have a good performance status, a life expectancy of greater than 6 months, and a PSMA [prostate-specific membrane antigen]–positive PET [positron emission tomography] CT using gallium-68 PSMA 11. That was 85% or 90% of patients, so most patients do. Patients were stratified by very standard criteria: metastases, ECOG performance status, etc. There were alternative primary end points of radiographic PFS [progression-free survival] or OS [overall survival]. Of 1179 patients screened, 1003 were positive, so 86.6% have the PSMA expression, so that’s the vast majority of patients. Ultimately, 831 patients were randomized of the 1003 who met criteria.
As we see, there was relatively low enrollment of Black African, African American, and Asian patients. Most patients received 1 prior androgen receptor pathway inhibitor and 1 prior taxane, so presumably just dosing. About 40% to 50% of patients received more than 1 of either the AR [androgen receptor] pathway inhibitor or taxane. One of the alternative primary end points was rPFS [radiographic PFS], which favored the lutetium 8.8 vs 3.6 months. There was a positive hazard ratio of 0.43. There are 2 points here: 1 is that lutetium works nicely, and the other is that when you use abiraterone, or after prior abiraterone or enzalutamide-docetaxel, it does nothing. It’s placebo. The rPFS benefit was preserved across most of the prespecified subgroups, not in the Black or African American or Asian populations, but in very small populations. The overall survival end point favors lutetium PSMA. There are 2 points: there’s a survival advantage, a good hazard ratio of 0.63, but if you’re not giving the lutetium, then survival is then less than a year in this population. These men are very far down the road. That’s always important to keep in mind as a data point.
When we look at the adverse events, you see a higher rate with the lutetium. The serious adverse events were a little under 10%; grade 3 to 5, about 8%; grade 5—that is, death—in just under 1%. In the treatment-emergent adverse events, what you see with lutetium is some myelosuppression, because so much of this will be taken up into the marrow and the bone, where there’s presumably prostate cancer metastases. Then you see dry mouth nausea, vomiting, and dry eyes because of the expression of PSMA and the salivary glands and the lacrimal glands. Then you see some excretion of lutetium into the GI [gastrointestinal] tract. There’s also excretion into the urinary tract. You see some renal effects and some potential cystitis impact on renal function. You don’t see a big signal in terms of secondary malignancies and no excess intracranial hemorrhage.
Transcript edited for clarity.