Durability of Remission from Pluvicto (Lutetium-177 Vipivotide Tetraxetan)
Remission from Pluvicto is not durable in the traditional sense—this is a disease control agent, not a curative therapy, with a median radiographic progression-free survival of 8.7 months and median overall survival of 15.3 months in heavily pre-treated mCRPC patients. 1
Understanding "Remission" in the Context of Pluvicto
The concept of durable remission does not apply to Pluvicto in the same way it might for curative therapies. Metastatic castration-resistant prostate cancer remains an incurable disease despite recent therapeutic advances. 2 Pluvicto provides disease control and symptom palliation rather than long-term remission.
Key Survival Metrics from Pivotal Trials
The VISION trial, which established Pluvicto's efficacy, demonstrated:
- Median radiographic progression-free survival: 8.7 months (versus 3.4 months with standard care alone; HR 0.40,99.2% CI 0.29-0.57, P<0.001) 1
- Median overall survival: 15.3 months (versus 11.3 months with standard care alone; HR 0.62,95% CI 0.52-0.74, P<0.001) 1
- Median time to first symptomatic skeletal event: 11.5 months (versus 6.8 months with standard care; HR 0.50,95% CI 0.40-0.62) 3
These data indicate that approximately half of patients will experience disease progression within 9 months of starting therapy. 1
PSA Response Patterns and Their Limitations
PSA responses do not equate to durable remission and should not be the sole measure of treatment success. 4 In clinical experience with Lu-177 PSMA therapy:
- 33-66% of patients achieve ≥50% PSA decline depending on the study population 5, 4
- PSA response after the first cycle predicts longer overall and progression-free survival 6
- However, PSA declines are often not durable, with many patients showing subsequent rises even while continuing therapy 2
The Prostate Cancer Clinical Trials Working Group emphasizes that time-to-event endpoints (overall survival, radiographic progression-free survival) are more meaningful than PSA changes alone in evaluating treatment durability. 4
Quality of Life Benefits: A More Relevant Outcome
Rather than focusing on remission duration, the more clinically relevant outcome is time to worsening of quality of life and symptoms. 3 The VISION trial demonstrated:
- Delayed time to worsening in FACT-P quality of life scores (HR 0.54,95% CI 0.45-0.66) 3
- Delayed time to worsening in pain intensity scores (HR 0.52,95% CI 0.42-0.63) 3
- 58% of patients with bone pain achieved complete resolution or reduced pain 5
These benefits typically last several months but are not permanent. 3
Factors Predicting Longer Disease Control
Certain baseline characteristics predict longer progression-free and overall survival with Pluvicto:
- Lower baseline alkaline phosphatase (<120 U/L) predicts longer OS and PFS 6
- Normal baseline hemoglobin predicts longer OS 6
- Lower baseline PSA (<51 ng/mL) predicts longer PFS 6
- Any PSA decline after the first cycle predicts longer OS and PFS 6
- Absence of visceral metastases is associated with better outcomes 6
Conversely, PSA progression ≥25% after the first cycle predicts shorter OS and PFS. 6
Treatment Duration and Re-treatment Considerations
Standard Pluvicto therapy consists of 4-6 cycles administered every 6 weeks, with each cycle delivering 7.4 GBq. 4, 7, 1 The VISION trial protocol allowed up to 6 cycles. 1
Re-treatment after initial progression has not been well-studied, and current guidelines do not provide clear recommendations on this approach. 4 Unlike docetaxel, where re-challenge may be considered in select patients who initially responded, 2 there is insufficient evidence to support routine re-treatment with Pluvicto after progression.
Realistic Expectations for Clinical Practice
Clinicians should counsel patients that Pluvicto provides a median of approximately 4 months additional survival benefit and 5 months additional progression-free survival compared to standard care alone. 7, 1 This represents meaningful but time-limited disease control in a heavily pre-treated population.
The median time to benefit is approximately 2-3 months, which is an important consideration when evaluating patients with very poor performance status or limited life expectancy. 7
Critical Pitfall to Avoid
Do not equate PSA responses with durable remission or cure. 2, 4 The AUA guidelines from 2004 explicitly warn that "a favorable effect on PSA may not be a surrogate for an antitumor effect" and emphasize the importance of measuring "the proportion of patients who do not develop metastatic disease at different time points after treatment" rather than focusing solely on PSA changes. 2
The goal of Pluvicto therapy is disease control and quality of life preservation, not cure. 2 Patients should understand that this is a palliative treatment that can extend survival and delay symptom progression, but progression is inevitable in virtually all cases.