So that provides a nice segue to the next question. I’m going to ask Dr. Tagawa, who was also an investigator in the VISION Trial and was a co-author on the New England Journal Medicine Paper on the primary results of the VISION Trial. So Scott, please tell us about the VISION trial, and then we can discuss how lutetium-177 PSMA-617 is going to be incorporated. How would you use this agent in the treatment of your patients with metastatic CRPC? And then, after that, we can talk about how this agent and similar agents or approaches are going to be moving to other earlier states of prostate cancer. So, let’s start with the VISION Trial first.
Sure. So the VISION Trial was designed in a way analogous to the trial. The first approved radionuclide leap led to an overall survival advantage radium 223 for metastatic CRPC in terms of most of the factors, in terms of study design other than imaging selection. So, the idea was to have a patient population that had all other drugs known to be a benefit. So chemotherapy, hormonal therapy, at least one of each was required, but if they were appropriate for radio-emission who got that before, if they were appropriate for PARP inhibitor, they should have got that before, etc., and then was in function as essentially an add-on. So patients got a standard of care, systemic therapy as limited and defined by the trial for safety reasons, but they got a standard of care therapy with or without lutetium PSMA-617, as Jeremie described what that is.
And the trial was designed with alternative primary endpoints of overall survival and radiographic progression-free survival. So, if only one of them were positive, the trial would be declared positive. And fortunately for patients, hopefully sometimes soon, both happen to be positive. So there was an overall survival benefit of nearly 40% in terms of hazard ratio, a radiographic progression pre-survival of 60%. So fairly impressive numbers for a heavily pretreated patient population, which I believe is not the optimal patient population for this drug to work well, as this was also mentioned by Dr. Calais, but fortunately, it worked. That is in tandem with a randomized phase II trial, a slightly different patient population, more heavily pre-selected based upon imaging, which we can go over if you want, but a head-to-head trial of patients with metastatic CRPC heavily pre-selected by imaging with prior docetaxel as it turned out about 9 in 10 had prior AR pathway inhibitor head-to-head against Cabazitaxel? And lutetium PSMA-617 was also better than Cabazitaxel? In terms of PSA endpoints, PSA response was the primary endpoint, also PSA progression for survival.
Importantly for the practicing physician that’s out there, there are adverse events that are associated with lutetium PSMA-617, and I don’t want to downplay them so much. I would say, overall, this treatment is very well tolerated, but it’s not like there’s none. So as in any positive study, patients gently in the positive arm are going to be exposed and follow longer for adverse events. So, you have to keep that in mind, but I categorize these in three major categories, constitutional, more fatigued, hematologic. So more myelosuppression, particularly in terms of thrombocytopenia, generally not with bleeding, and then kind of the GI tract starting from the mouth in terms of dry mouth as well, some nausea, generally low grade and generally reversible, but those are adverse events that have been described with this more than control.
Despite that having more adverse events in a presentation at ESMO 2021, there was a significant benefit in terms of time deterioration of patient report outcome. So despite more adverse events, because likely of better cancer control, the time to deterioration of quality of life, brief pain inventory, as well as symptomatic [inaudible 00:41:37] events was all in favor of the lutetium PSMA-617 treatment arm.
Those are very, very good information for our colleagues out there who may be listening.