Pluvicto shows clinically meaningful and highly statistically significant rPFS benefit in patients with PSMA-positive metastatic castration-resistant prostate cancer in the pre-taxane setting

“The rPFS data are impressive and the treatment effect is comparable with what was observed in the VISION trial,” said Dr. Oliver Sartor, PSMAfore Co-Principal Investigator, Chairman of the Trial Steering Committee and adjunct professor in the Department of Urology at Tulane University School of Medicine, New Orleans, LA, one of the many sites where the trial was conducted. “We look forward to a future where Pluvicto may be a viable therapy for patients in need of alternative, earlier options.”

“These promising results from PSMAfore could change the treatment paradigm for advanced prostate cancer by allowing patients to potentially avoid or delay taxane-based chemotherapy, which carries a heavy burden of side effects,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development at Novartis. “While data collection for overall survival continues, the consistency of the benefit observed on other clinically meaningful efficacy endpoints, together with improved quality of life and favorable safety profile, show the potential of Pluvicto for taxane-naïve patients with mCRPC.”

The trial met its primary endpoint of rPFS2 with a 59% reduction in the risk of radiographic disease progression in patients with Pluvicto versus a change of ARPI. Using a data cut off with a median of 8.6 months longer study follow-up, an updated rPFS analysis (HR 0.43; 95% CI: 0.33, 0.54) demonstrated a consistent clinical benefit in patients with Pluvicto versus a change in ARPI, more than doubling time to radiographic disease progression (12.0 months vs. 5.6 median months).

Patients on Pluvicto also showed improved quality of life , maintaining their FACT-P total score for 3 months longer than a change in ARPI (7.5 vs. 4.3 months), with a delay in worsening pain (BPI-SF) of 5.0 versus 3.7 months. Other clinically meaningful efficacy endpoints also favored Pluvicto, with a PSA decline of at least 50% being greater than 2.5X more frequent with Pluvicto than with a change in ARPI1.

At the second interim OS analysis with 45% of events, the pre-specified crossover-adjusted OS analysis demonstrated a hazard ratio of 0.80 (95% CI: 0.48, 1.33). The unadjusted intent-to-treat OS analysis was confounded as 84% of patients who discontinued ARPI due to radiographic progression crossed over to receive Pluvicto. The trial will continue to assess OS, with the next interim OS analysis expected in 2024.

The trial demonstrated a favorable safety profile with 6 cycles of Pluvicto.

The most frequently reported all-grade AEs for Pluvicto were primarily Grade 1–2 and included dry mouth (57.3%), asthenia (31.7%), nausea (31.3%), anemia (24.2%) and fatigue (22.9%). Currently, patients diagnosed with metastatic prostate cancer have a 5-year survival rate of approximately 30% and there remains an urgent need for treatment options for patients who have disease progression despite the current standard of care.

About the PSMAfore Study : PSMAfore (NCT04689828) is a Phase III, open-label, multi-center, 1:1 randomized study comparing the efficacy and safety of Pluvicto to a change in ARPI (abiraterone or enzalutamide) in patients with PSMA-positive mCRPC who have not been exposed to a taxane-containing regimen. Patients enrolled must have progressed only once after receiving a second-generation ARPI (abiraterone, enzalutamide, darolutamide or apalutamide). Patients randomized to the change in the ARPI arm were allowed to crossover to receive Pluvicto upon confirmation of radiographic progression by blinded independent central review (BICR). There were 469 participants enrolled in the study. The primary endpoint is rPFS, defined as the time from randomization to radiographic progression by PCWG3-modified RECIST v1.1 (as assessed by BICR) or death. The key secondary endpoint of OS is defined as the time from date of randomization until the date of death due to any cause. The pre-specified crossover-adjusted OS analysis was performed using the rank-preserving structural failure time (RPSFT) model to adjust for crossover.