PLUVICTO is the first and only PSMA-targeted RLT to significantly extend overall survival in a phase 3 mCRPC trial

BSOC, best standard of care; mCRPC, metastatic castration-resistant prostate cancer; OS, overall survival; PSMA, prostate-specific membrane antigen; RLT, radioligand therapy.

Post hoc exploratory subgroup analysis^2,3 

^a Of the 831 patients, 8 had received more than 2 taxanes previously.²

Limitations: No formal statistical testing was planned for this exploratory subgroup analysis; therefore, there was no prespecified statistical procedure controlling for type 1 error. These results should be interpreted with caution. 

Patients treated with PLUVICTO + BSOC had a statistically significant improvement in rPFS: 8.7 months vs 3.4 months with BSOC alone³

Interpretation of the magnitude of the rPFS effect was limited due to a high degree of censoring from early dropout in the control arm.

HR, hazard ratio; rPFS, radiographic progression-free survival.

PLUVICTO + BSOC significantly improved overall response rates vs BSOC alone^1,4

CR, complete response; ORR, overall response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.

ORR=CR + PR.

^a ORR is reported as a measure of response in soft tissue, lymph node, or visceral lesions.^4
b Patients with evaluable disease from baseline.^4
c Stratified Wald's Chi-square test 2-sided P value.^1,4 

46% of patients who received PLUVICTO + BSOC had a PSA decline ≥50% vs 7% of patients who received BSOC alone⁴

Proportion of subjects who are PSA responders, defined as patients who achieved a ≥50% decrease from baseline that is confirmed by a second PSA measurement ≥4 weeks later.

PSA, prostate-specific antigen.

^a Odds ratio 11.19 (95% CI, 6.25-20.04).
^b Odds ratio 23.62 (95% CI, 8.57-65.11).

• Data are from patients with available PSA data allocated to PLUVICTO + BSOC or BSOC alone

• The proportion of patients with any decrease in best percentage change from baseline was 71.5% with PLUVICTO + BSOC, 35.5% with BSOC alone

• Data are from patients randomized after implementation of enhanced study-site education measures, N=581. PSA decline was assessed at the nominal 5% level; eg, no alpha control was applied. Increases greater than 100% are truncated to 100%

Trial design

PLUVICTO was studied in VISION, the largest international phase 3 trial of a targeted RLT

The VISION trial was a randomized, multicenter, active-control study comparing PLUVICTO + BSOC vs BSOC alone^1,2

• This prospective, open-label study enrolled 831 men with PSMA+ mCRPC who had disease progression on at least 1 ARPI and 1 or 2 taxane regimens

• VISION was an active-controlled study: Participants were randomized to receive PLUVICTO + BSOC (physician's choice as defined below) or BSOC (physician's choice) alone

Pivotal VISION Phase 3 trial design

ARPI, androgen receptor pathway inhibitor; ECOG PS, Eastern Cooperative Oncology Group performance status; LHRH, luteinizing hormone-releasing hormone; PSMA+, prostate-specific membrane antigen positive.

^a To be declared positive, the VISION study was required to reach statistical significance on the primary analysis of rPFS or OS, not both end points.

Stratification factors^1,4

• Inclusion of ARPI at time of randomization (yes vs no)

• Baseline lactate dehydrogenase (LDH) (≤260 IU/L vs >260 IU/L)

• Presence of liver metastases (yes vs no)

• ECOG PS (0-1 vs 2)

The phase 3 VISION trial enrolled men with PSMA+ mCRPC who had progressed on ARPI and taxane therapy

Baseline patient characteristics were well balanced across the treatment and control arms*

PET, positron emission tomography; PFS, progression-free survival.

*The analysis set for imaging-based PFS included patients who underwent randomization on or after March 5, 2019, the date on which trial-site education measures were implemented to reduce the incidence of withdrawal in the control group. Percentages may not total 100 because of rounding.
^a ECOG PS scores range from 0 to 5, with higher numbers indicating greater disability.
^b Data were missing for a very small number of patients.
^c Scores on the Gleason scale range from 2 to 10, with higher scores indicating a worse prognosis. A score of 8 to 10 indicates high-grade cancer. In the remaining patients whose score was known, the Gleason score was 2 to 7 (intermediate- or low-grade cancer).
^d ARPIs were defined as enzalutamide, abiraterone, and apalutamide.
^e Taxanes were defined as cabazitaxel, docetaxel, and paclitaxel. Of the 831 patients, 8 (1.0%) had received more than 2 taxanes previously. Overall, the reasons for the last taxane therapy were therapeutic use in 559 of 831 patients (67.3%), adjuvant therapy in 109 (13.1%), unknown in 106 (12.8%), neoadjuvant therapy in 33 (4.0%), maintenance therapy in 17 (2.0%), other in 5 (0.6%), and prophylaxis in 2 (0.2%). The use of taxanes was well balanced between treatment groups in both analysis sets.