The study is the VISION trial, it’s a phase III study in which a drug called Lutetium-177-PSMA-617 was added to the standard of care versus the standard of care alone in men with metastatic castration resistant prostate cancer. These men all had progressive disease despite androgen receptor pathway inhibitors and despite one to two different regimens of chemotherapy. So these patients had little in the way of standard treatment options.
About the drug, PSMA-617 is a small molecule that has high affinity for the external domain of prostate specific membrane antigen, or PSMA, which is expressed in over 80% of men with metastatic CRPC. The payload for this targeting molecule was a beta emitter called lutetium-177 and hence the moniker lutetium-177-PSMA-617 for the drug.
This was a randomised trial in which men who had the features that I just described, metastatic CRPC refractory to both an androgen receptor pathway inhibitor and one to two regimens of chemotherapy, were screened for this study using a PSMA PET-CT that was gallium-68 PSMA-11. So if these men had positive disease on that PSMA PET scan they were eligible for this trial, providing that they met other criteria.
What was interesting about the design of this trial is basically everybody before they were randomised got assigned a standard of care by their treating physician. That could be pretty much anything that was available for this group of patients who, granted, had few standard treatments available but it could not include chemotherapy, radio-targeted therapy in the form of radium-223, immunotherapy or investigational therapy because on a 2:1 basis men would be assigned to receive lutetium-PSMA as well and we don’t have safety data on those specific combinations.
The treatment itself was four cycles of lutetium-PSMA-617 and that could be expanded to six cycles in men who had responsive disease but who had residual disease. The treatment is given as an outpatient by vein every six weeks.
We found that the patients who received the lutetium in addition to the standard of care had an improved survival or a lower risk of death by 38%. That translated into an absolute difference of the medians of four months. The patients who were on the control arm had an 11.3 month median overall survival and the patients who received lutetium had a 15.3 month median overall survival. The hazard ratio was 0.62 and the p-value was less than 0.001.
The other primary endpoint, there were two primary endpoints, one was overall survival the other was radiographic progression free survival. rPFS was improved by 60% and that resulted in a five month improvement in overall survival from 3.6 months as a median rPFS to 8.8 months rPFS, so a five month improvement in rPFS. Sorry if I misspoke before. That was in the entire overall survival analysis set. The median improvement in rPFS for the subset of patients specifically followed for rPFS was, again, a five month improvement in rPFS, improving from 3.4 months to 8.7 months.
These patients with ARPI refractory and chemotherapy refractory disease do have very few standard treatment options. So what this trial introduces is a new family of therapeutics for these patients which can improve overall survival. So that always, in and of itself, is a very important introduction. It allows men who otherwise would not have a drug to improve their survival, to have access now to a drug that will do so, provided that the therapy is FDA approved or internationally regulatorally approved.
The other thing is that it does introduce the opportunity to combine this therapy with other treatments in order to optimise the existing regimens that we have for metastatic CRPC. It also introduces an opportunity to treat patients earlier than was seen in the VISION trial which is the latest point in the natural history of the disease. So it really benefits patients on multiple levels.
The key findings of this study were that for the two primary endpoints of the study, which were overall survival and radiographic progression free survival, this study was a success. In terms of overall survival patients had a reduced risk of death of 38% with an improvement of median overall survival of four months from 11.3 months to 15.3 months and the p-value for overall survival was 0.001. In regards to the second primary endpoint which was rPFS, or radiographic progression free survival, there was an improvement in rPFS by 60% with a hazard ratio of 0.4, a p-value of 0.001 and the improvement in median rPFS was five months from 3.4 months to 8.7 months.