PSMA-Positive mCRPC and the VISION Trial

EP: 1.Initial Risk Stratification of Localized Prostate Cancer

EP: 2.Defining PSMA-PET Scans for Prostate Cancer

EP: 3.Case 1: Metastatic Castrate-Resistant Prostate Cancer

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EP: 4.PSMA-Positive mCRPC and the VISION Trial

EP: 5.Lutetium-PSMA-617 for Prostate Cancer Treatment

EP: 6.Radium-223 and the ALSYMPCA Trial

EP: 7.Case 2: Metastatic Hormone-Sensitive Prostate Cancer

EP: 8.Reviewing Data from the CARD Trial

EP: 9.mCRPC: The TheraP Trial

EP: 10.Therapy Sequencing and Patient Selection in Prostate Cancer Treatment

EP: 11.Case 3: Metastatic Castrate-Resistant Prostate Cancer

EP: 12.Lutetium-PSMA-617 and Novel Agents in Prostate Cancer

Alicia Morgans, MD, MPH: Let’s move on to some data that may describe 1 of the potential options for patients like this. Ulka, would you mind telling us about the VISION trial?

Ulka Vaishampayan, MD: The VISION trial is a phase 3 open-label study comparing protocol-permitted standard of care plus or minus 177Lutetium-PSMA-617, for PSMA [prostate-specific membrane antigen]–positive metastatic CRPC [castration-resistant prostate cancer]. For the eligibility criteria for this study, all patients had metastatic CRPC. They were required to receive at least 1 androgen receptor pathway inhibitor agent and at least 1 taxane-based regimen. Up to 2 prior taxane regimens were allowed, and protocol-permitted standard of care that was planned before randomization excluded chemotherapy, radium 223, or any investigational drugs or immunotherapy. It allowed second-line hormonal therapies, including androgen receptor pathway inhibitors. The performance status had to be 0 to 2, with life expectancy of more than 6 months, and they had to have PSMA-positive metastatic CRPC. Phil, can you comment on the eligibility criteria based on imaging for this study?

Phillip J. Koo, MD: PSMA positivity is tricky…. When they were trying to design this, they tried to make it as easy and open as possible. This idea of PSMA positivity was defined as PSMA uptake in the lesion greater than liver, so it kept it simple. When they looked back, only 13% of patients screened failed because they had PSMA-negative lesions. This is just the baseline. This is the starting realm. It cast a wide net and made it easy to define those patients who are PSMA positive vs PSMA negative.

Ulka Vaishampayan, MD: Thank you. That’s important because we’re reading scans and deciding on patients for this therapy, and that’s a critically important point. These patients were basically randomized in a 2-to-1 fashion to a standard of care plus 177Lutetium PSMA, given every 6 weeks at 7 GBq [gigabecquerel] dosage for 4 cycles. These were sometimes increased to 6, depending on patient tolerability response, etc. The standard arm had protocol-permitted standard of care, which excluded chemotherapy, immunotherapy, radium-223, and investigational drugs. Palliative radiation externally was allowed. The primary end point of the study was radiographic progression-free survival as well as overall survival. The secondary end point was time to first symptomatic skeletal event and resist response rates in the measurable disease patients, and disease control rate was also checked. The study design included doing scans about every 8 weeks. Every 12 weeks a follow-up was required. Toxicity checks and blinded independent central review were done for the scans before progression was determined.

Here are the screening enrollment and baseline characteristics of the patients: 1000-plus patients were screened, and about 13% were screened out because they did not having adequate PSMA expression on the scan. Finally, about 82.9% of the patients were randomized. Baseline characteristics were pretty well balanced across the 2 treatment arms, and ECOG [performance] status sites of disease and previous cancer treatments were the stratification factors. It had a fairly low enrollment of patients who are of African American ethnicity, 6.6%, and Asian patients consisted of 2.4% of the accrued population. Patients received a median of 1 prior antigen receptor pathway inhibitor, and the range was 1 to 5 with 1 prior taxane, 1 to 3. About 40% to 50% of patients received more than 1 AR [androgen receptor] inhibitor or taxane.

If you look at the study timeline, there was an early dropout in patients who were randomized to standard of care. Because of that, there was an increase in the sample size. The study started in June 2018, and additional measures were implemented to make sure patients were retained on the arm they were randomized to. In October 2019, which was fairly quickly, within about a year and a half total, the study completed accrual.

In the VISION trial, the primary end points were based on radiologic progression-free survival [rPFS] and overall survival. As you can see, the Lutetium-PSMA improved radiologic progression-free survival. The improvement was statistically significant over the standard of therapy alone. The median with Lutetium-PSMA-617 was 8.7 months rPFS, compared with 3.4 months with standard therapy. Hazard ratio was 0.4, and P value was statistically significant. Similarly for overall survival, Lutetium-PSMA-617 showed an improvement in overall survival. That was significantly better than standard therapy. The median was 15.3 months with Lutetium-PSMA and 11.3 months with the standard of care. Hazard ratio was 0.62, and P value was less than .001.

Lutetium PSMA showed serious adverse events in about 9.3% vs 2.4% serious adverse events on standard of care. The main adverse effects that were seen were cytopenia. Grades 3 to 5 cytopenias were seen in 23.4% with Lutetium PSMA, 6.8% on standard of care. The rates of anemia were 12.9% of the patients with Lutetium PSMA. Dry mouth was not seen in grades 3 to 5, but in all grade toxicities 1 to 2, 39.3% of the patients had a dry mouth with Lutetium PSMA. Nausea and emesis was also seen in 39.3%. Renal effects were seen in 8.7%. There are some second primary malignancies reported in 2.1% of the patients with Lutetium PSMA therapy, and 1% of the patients were on standard of care. Intracranial hemorrhage was seen in a small proportion, 1.3% and 1.5%, so not really different between the 2 arms.

Alicia Morgans, MD, MPH: Thank you for such a thorough discussion of the VISION data. This was something that we’d been excited to hear about, and I’m glad we have these data. Of course, this led to FDA approval pretty recently.

Transcript edited for clarity.