Health-related Quality of Life and Pain Outcomes

177-Lu-PSMA in Metastatic Castration-Resistant Prostate Cancer

VISION Trial: Phase 3 Randomized Study

Fizazi K, et al. Lancet Oncol 2023

Background

 

  • mCRPC remains an incurable disease despite therapeutic advances
  • Patients have high risk of impaired health-related quality of life (HRQOL) and increased mortality
  • Up to 90% have bone metastases which significantly impact HRQOL
  • [177Lu]Lu-PSMA-617 previously showed improved rPFS and OS in VISION trial
  • This analysis examines impact on HRQOL, pain and symptomatic skeletal events

 

  • Phase 3, open-label, randomized trial (2:1)
    • 84 Centers
  • N=581 enrolled after March 2019:
    • 385 [177Lu]Lu-PSMA-617 + standard of care
    • 196 standard of care alone
  • Key Eligibility:
    • Progressive PSMA+ mCRPC
    • Prior AR pathway inhibitor and 1-2 taxanes
    • ECOG PS 0-2
    • PSMA-positive tumors on Ga-68 PSMA-11 PET/CT
    • No eligibility for additional chemotherapy
    • Life expectancy ≥6 months
  • Treatment:
    • 177Lu-PSMA-617: 7.4 GBq IV q6wk x 4-6 cycles
    • Standard of care: hormonal therapy, bone-targeted agents, supportive care

VISION Trial Design

Screening
Assess eligibility, 68Ga-PSMA-11 PET/CT scan
↓
PSMA-positive cancer?
No
↓
Screen Failure
Yes
↓
Randomization (2:1)
Investigational Arm
177Lu-PSMA-617 + Best Supportive/Standard Care
7.4 GBq every 6 weeks, max 6 cycles
Control Arm
Best Supportive/Standard Care Alone
↓
End of Treatment Visit
30 days after last treatment
↓
Long-term Follow-up
Every 3 months for 24 months

Patient Population

Primary Outcomes

Safety

  • Higher grade 3-4 hematologic adverse events with Lu-PSMA-617:
    • Anemia: 15% vs 6%
    • Thrombocytopenia: 9% vs 2%
    • Lymphopenia: 51% vs 19%
  • 5 treatment-related deaths in Lu-PSMA-617 arm:
    • Pancytopenia (n=2)
    • Bone marrow failure (n=1)
    • Subdural hematoma (n=1)
    • Intracranial hemorrhage (n=1)
  • Renal function remained stable

Safety

Safety

Hemaglobin

Platelets

Creatinine

Symptomatic Skeletal Events

  • Median time to first SSE or death:
    • Lu-PSMA: 11.5 months
    • Control: 6.8 months
    • HR 0.50 (95% CI 0.40-0.62)
  • SSE events:
    • Lu-PSMA: 60/385 (16%)
    • Control: 34/196 (17%)
  • Benefit seen regardless of bone-targeted therapy use
  • Most common SSE: radiation for bone pain

Symptomatic Skeletal Events

Symptomatic Skeletal Events

Quality of life Endpoints

 

  • Patient-Reported Outcomes (PROs):
    • FACT-P (Functional Assessment of Cancer Therapy-Prostate)
    • EQ-5D-5L utility score
    • Brief Pain Inventory-Short Form (BPI-SF)
  • Time to first symptomatic skeletal event

 

  • PROs assessed at:
    • Baseline
    • Day 1 of each cycle
    • End of treatment
  • Safety/adverse events also evaluated

Endpoints

EQ-5D-5L (European Quality of Life (EuroQol) – 5 Domain 5Level scale)

Key Results - HRQOL

 

  • Delayed time to worsening with Lu-PSMA-617 vs SOC for:
    • FACT-P total score
      • Lu-PSMA: 5.7 vs Control: 2.2 ​(HR 0.54; 95% CI 0.45-0.66)
    • BPI-SF pain intensity
      • 6.9 vs Control: 2.6 (HR 0.52; 95% CI 0.42-0.63)
    • EQ-5D-5L utility score
      • 1.0 vs Control: 0.5 (HR 0.65; 95% CI 0.54-0.78)

 

  • Benefits seen across all FACT-P domains
  • Similar results in prespecified and post-hoc analyses
  • Consistent effects with/without including disease progression/death

Key Results - FACT-P

  Time to worsening of 10 points or more in the FACT-P score, clinical disease progression, or death

Key Results -

 Time to worsening of at least 30% or at least 2 points in the BPI-SF scale,

clinical disease progression, or death

Key Results -

C) or anincrease of at least 2 points inthe BPI-SF scale

Key Results -

(post hoc; D).Time to worsening inEQ-5D-5L utility score, defined as the time to any decrease inutility score relative to baseline; or no change in score from baseline 

Key Results -

prespecified; E) Time to worsening inEQ-5D-5L utility score, defined as the time to any decrease inutility score relative to baseline; or no change in score from baseline

Key Results -

decrease in score of at least 0·10 points from baseline(post hoc; F)

Conclusions

 

  • [177Lu]Lu-PSMA-617 + standard of care improved multiple aspects of HRQOL:
    • Delayed time to worsening of FACT-P scores
    • Delayed pain progression
    • Delayed symptomatic skeletal events
  • Manageable safety profile with expected hematologic toxicity
  • Results support use in mCRPC patients previously treated with AR pathway inhibitors and taxanes

Discussion Points

 

  1. How do these QOL outcomes impact the positioning of Lu-PSMA-617 in the treatment landscape?
  2. What are implications of improved skeletal-related events for patient management?
  3. How should the hematologic toxicity profile inform patient selection?
  4. What are key considerations for implementing Lu-PSMA-617 in clinical practice?
  5. What questions remain about optimal use of Lu-PSMA-617?