Oliver Sartor, MD: We have excellent data from the VISION trial regarding the eligibility of patients after PSMA [prostate-specific membrane antigen] PET [positron emission tomography]. In the VISION trial, there were positive and negative selection criteria. For the positive selection criteria, you needed to have PSMA PET uptake in a metastatic lesion greater than the uptake in the liver. That was present in 90%-plus of patients. On the other hand, patients were excluded if they had PSMA-negative PET lesions that were found to be present on cross-sectional imaging, such as CT scan.

Imagine for a second that you had a 2-cm liver metastasis on the CT scan, while on the PSMA PET scan, that was a negative lesion with no uptake. That patient would be excluded. It turns out that when we used the inclusion and exclusion criteria, we excluded about 13% of patients. A little over a thousand patients were scanned in VISION, so that 13% is a pretty big number. These are patients who already had prior treatment with agents such as abiraterone; enzalutamide; at least 1 taxane, like docetaxel; and often 2 taxanes, like docetaxel and cabazitaxel. Taken together, we know that this phenotypic marker, PSMA, can be utilized to select patients for treatment with PSMA lutetium–type therapies.

There are significant inclusion and exclusion criteria within the VISION trial that need to be understood in order to interpret the data. First, the patients had to have metastatic disease on conventional imaging. That’s the CT scan and bone scan. They also had to be castration resistant. They must have failed prior therapy with a novel androgen axis–targeted agent, which was typically abiraterone, enzalutamide, or both. They also had to have failed at least 1 taxane, up to 2. In prostate cancer, docetaxel and cabazitaxel are typically the 2 taxanes utilized. About 40% of the patients had 2 prior taxanes and still had progressive disease.

In addition, the patients had to be PSMA PET–positive in the metastatic lesions and not have any PSMA PET–negative lesions that would have excluded them from the trial. In addition, you had to have adequate hematologic function, renal function, liver function, etc, and a performance status of 0 to 2. Taken together, there are variety of inclusion and exclusion criteria that were important in the selection of patients in VISION.

After the patients were selected, they were randomized 2:1, and the randomization was to the standard of care or standard of care plus lutetium-177. The 2:1 randomization meant 2 of the patients would be getting lutetium and 1 would be getting the standard of care alone. That’s standard of care plus or minus, so what’s the standard of care? Most of the patients received standard of care that was another hormonal agent, even though many of them had already had agents like abiraterone or enzalutamide. That was the typical standard of care used. You could also use glucocorticoids, bisphosphonates, external beam radiation, or SBRT [stereotactic body radiation therapy]. Any of those were allowed. Chemotherapy wasn’t allowed.

There were 2 coprimary end points. They were alternate primary end points, if you will. One was rPFS [radiographic progression-free survival], and the other was overall survival [OS]. Then there was a series of secondary end points, with things like tumor shrinkage. The bottom line is that it was a very positive trial. With overall survival, the hazard ratio was 0.62, and the confidence intervals didn’t even get close to 1. There was about a 4-month prolongation of overall survival at median, and the rPFS was prolonged with a hazard ratio of 0.40. The P value was less than 0.001. It’s unequivocally positive on both rPFS and OS.

How was it tolerated? There were issues related to dry mouth that were present as a result of the PSMA lutetium, some additional fatigue, some degree of anemia, and mild thrombocytopenia. It was quite tolerable and manageable overall. Overall, this was a positive trial. The overall survival end point was clearly positive, with a hazard ratio of 0.62 and 4-month prolongation in this very difficult-to-treat patient population. Remember, they already had abiraterone, enzalutamide, cabazitaxel, and docetaxel. These were heavily pretreated patients.

You can see from the New England Journal of Medicine manuscript that you can anticipate that we’ll end up with an FDA approval in the not-too-distant future, sometime in 2022. Hopefully it’ll be approved in the spring. That’s anticipated. I don’t have any particular insights into exactly when the FDA will approve it. Regardless, with this type of safety profile and the overall survival end point, I feel like this therapy will be available to patients in 2022.

When we looked at the initial analyses, there were predominantly objective measures like radiographic progression-free survival and overall survival. At ESMO [European Society for Medical Oncology Congress] 2021, there was an update that presented the health-related quality of life, and in particular, the FACT-P [Functional Assessment of Cancer Therapy–Prostate] scores that were measured over time in these patients in both the control arm and the active treatment arm with PSMA lutetium. It was shown unequivocally that there was a significant improvement with regard to the time to deterioration in health-related quality of life. There was also a significant improvement with regard to the time to deterioration in pain scores. There was improvement in objective measures, like PSA [prostate-specific antigen] declines, tumor shrinkages, rPFS, and OS. There was also clear improvement in the health-related quality of life parameters that were assessed and reported at ESMO 2021.

Transcript edited for clarity.