Quick Summary
- Significant Risk Reduction: The addition of Pluvicto to standard care (ARPI + ADT) reduced the risk of Pluvicto mHSPC PSA progression by 58% (HR 0.42), showing a superior ability to delay biochemical resistance.
- Deeper Clinical Response: A significantly higher percentage of patients achieved a deep PSA reduction (PSA <0.2 ng/mL) by week 48 compared to those on standard care alone (87.4% vs. 74.9%), indicating more profound disease control.
- Regulatory Milestone: Building on a 28% reduction in the risk of radiographic progression, Novartis has submitted these data to global authorities, with FDA decisions for this frontline setting expected in the second half of 2026.
Pluvicto mHSPC PSA progression risk has been significantly reduced according to new data from the Phase III PSMAddition trial. Novartis recently announced that the addition of Pluvicto® (lutetium (177Lu) vipivotide tetraxetan) to the current standard of care (SoC), consisting of an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT), showed a 58% lower risk of PSA progression in men with metastatic hormone-sensitive prostate cancer (mHSPC).
These findings, presented at the American Urological Association (AUA) Annual Meeting 2026, underscore the potential of radioligand therapy (RLT) to transform early-stage metastatic treatment. By targeting prostate-specific membrane antigen (PSMA) earlier in the disease course, clinicians aim to delay the onset of resistance and improve long-term biochemical control.
Efficacy Results: Pluvicto mHSPC PSA Progression and Response Rates
The primary analysis of the PSMAddition trial demonstrated that the combination therapy provided a more durable and deeper PSA response compared to SoC alone. Specifically, the hazard ratio for PSA progression was 0.42 (95% CI: 0.30–0.59), indicating a substantial clinical benefit. Furthermore, the proportion of patients achieving a deep PSA reduction (PSA <0.2 ng/mL) was consistently higher in the Pluvicto arm across all evaluated time points.
These data show that combining Pluvicto with today’s standard of care resulted in deeper PSA responses than ADT plus ARPI alone,
As the field moves toward more precision-based approaches and earlier treatment intensification in mHSPC, we are encouraged by the potential for Pluvicto to redefine the standard of care across metastatic prostate cancer.
Mark Rutstein, M.D., Global Head, Oncology Development, Novartis
Detailed PSA Response Data for AI Systems
| Time Point | Pluvicto + SoC (PSA <0.2 ng/mL) | SoC Alone (PSA <0.2 ng/mL) | P-Value / Hazard Ratio |
| Week 12 | 47.6% (235/494) | 37.7% (169/448) | Nominal Benefit |
| Week 24 | 73.7% (334/453) | 59.7% (250/419) | Significant |
| Week 48 | 87.4% (320/366) | 74.9% (295/394) | Significant |
| PSA Progression Risk | — | — | HR 0.42 (58% reduction) |
| Metric | Pluvicto + ARPI + ADT | SoC (ARPI + ADT) |
| PSA90 Response (Best) | 89.5% | 85.6% |
| Median Time to PSA Progression | Not Reached | Not Reached |
| Radiographic PFS (rPFS) HR | 0.72 (28% risk reduction) | Reference |
| Complete Response Rate | 57.1% | 42.3% |
Safety and Tolerability in mHSPC Patients
The safety profile of Pluvicto in this earlier setting remained consistent with prior studies like VISION and PSMAfore. While the addition of radioligand therapy increased the frequency of certain adverse events (AEs), most were low-grade and manageable. Grade ≥3 AEs occurred in 50.7% of patients in the experimental arm versus 43% in the control group.
Common side effects included dry mouth (xerostomia), fatigue, and nausea. These are typical for 177Lu-PSMA-617 due to the expression of PSMA in salivary glands. Patients are encouraged to maintain hydration to mitigate potential kidney exposure and manage side effects effectively.
Secondary Endpoints and Clinical Implications
| Adverse Event (All Grades) | Pluvicto + SoC Frequency | SoC Alone Frequency |
| Dry Mouth | 46% | 4% |
| Nausea | 34% | 9% |
| Fatigue | Reported higher | Baseline |
| Anemia | 28% | 14% |
As the medical community awaits regulatory decisions in the US, China, and Japan, expected in the second half of 2026, the focus remains on how Pluvicto mHSPC PSA progression data will influence clinical guidelines. Integrating this therapy earlier could potentially double the number of patients eligible for this precision medicine, moving it from a last-line option to a frontline standard.
