Initial Experience with [177Lu]Lu-PSMA-617 After Regulatory Approval for Metastatic Castration-Resistant Prostate Cancer: Efficacy, Safety, and Outcome Prediction | Journal of Nuclear Medicine

Andrei Gafita, Andrew Voter, Somya Shesadri, Avery Spitz, Catherine H. Marshall, Steven P. Rowe, Mark C. Markowski, Martin G. Pomper, A. Cahid Civelek, Michael A. Carducci, Samuel R. Denmeade, Jeffrey Young, Kenneth J. Pienta, Channing J. Paller and Lilja B. Solnes

Journal of Nuclear Medicine November 2024, 65 (11) 1724-1730;  

DOI: https://doi.org/10.2967/jnumed.124.267723

 

This figure summarizes the key findings from the study of Lu-PSMA therapy for advanced prostate cancer in a visual format. Let me break it down:

The figure is divided into three main sections:

1. Left Section - Safety Profile & Efficacy:

- Safety shows the percentage of side effects:

  * Anemia (low red blood cells): 12%
  * Thrombocytopenia (low platelets): 4%
  * Neutropenia (low white blood cells): 1%
  * Xerostomia (dry mouth): 23%

- Efficacy measures:

  * 41% of patients had PSA response
  * PSA-PFS (progression-free survival): 4.1 months
  * OS (overall survival): 13.7 months

2. Middle Section - Shows different patient response groups:

- Separates patients into different categories with survival times
- Shows response rates varying from around 19% to 95%

3. Right Section - SelectPSMA Results:

- Compares patients predicted to respond (51% response rate) vs non-responders (6% response rate)
- Shows the difference in survival times between these groups
- Demonstrates how the AI tool might help predict which patients will benefit most

The different colored bars and numerical values help visualize the differences in outcomes between different patient groups and highlight the potential value of using SelectPSMA for patient selection.

Would you like me to elaborate on any specific part of this figure?

Simple Summary

This study looked at a newer treatment called Lutetium-PSMA (or Lu-PSMA) for advanced prostate cancer that has stopped responding to hormone therapy. The treatment was approved by the FDA, and doctors wanted to see how well it works in real-life medical practice, not just in clinical trials.

Here's what they found:

1. How well it worked:

- About 4 in 10 patients saw their PSA levels drop significantly
- On average, the treatment kept the cancer under control for about 4 months
- Patients lived an average of about 14 months after starting treatment

2. Side effects were generally manageable:

- The most common side effect was temporary dry mouth, affecting about 1 in 4 patients
- Some patients experienced low blood counts, but serious cases were rare
- Overall, the treatment was well-tolerated by most patients

3. Predicting who might benefit:

- Doctors used a special computer program to look at imaging scans
- This helped them identify which patients might respond better to the treatment
- This could help future patients and their doctors make better treatment decisions

Remember: These results are from one medical center, and your own experience might be different. Always discuss your specific situation with your healthcare team, as they can best advise you about whether this treatment might be right for you.

Clinical Summary

Let me help analyze this important clinical research article about [177Lu]Lu-PSMA-617 therapy in metastatic castration-resistant prostate cancer (mCRPC).

Key Findings:

1. Efficacy:

- PSA response (≥50% decline) achieved in 41% of patients (30/74)
- Median PSA Progression-Free Survival: 4.1 months
- Median Overall Survival: 13.7 months

2. Safety Profile:

- Grade ≥3 adverse events:

  * Anemia: 12%
  * Thrombocytopenia: 4%
  * Neutropenia: 1%

- Xerostomia (dry mouth): 28% (transient)

3. Outcome Predictors:

- Aggressive-variant prostate cancer genes correlated with shorter PSA PFS
- AI analysis (SelectPSMA) showed promising predictive value:
  * Predicted non-responders had:

    - Lower PSA response rates (6% vs 51%)
    - Shorter PSA PFS (1.3 vs 6.3 months)
    - Shorter OS (6.3 vs 14.5 months)

The findings suggest that [177Lu]Lu-PSMA-617 demonstrates meaningful clinical activity with manageable toxicity in real-world settings, consistent with clinical trial results. The AI-based imaging analysis tool (SelectPSMA) shows potential for improving patient selection.

This represents important real-world validation of this therapy following FDA approval, though the authors note that larger cohort validation is needed.

Visual Abstract

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This figure summarizes the key findings from the study of Lu-PSMA therapy for advanced prostate cancer in a visual format. Let me break it down:

The figure is divided into three main sections:

1. Left Section - Safety Profile & Efficacy:
- Safety shows the percentage of side effects:
  * Anemia (low red blood cells): 12%
  * Thrombocytopenia (low platelets): 4%
  * Neutropenia (low white blood cells): 1%
  * Xerostomia (dry mouth): 23%

- Efficacy measures:
  * 41% of patients had PSA response
  * PSA-PFS (progression-free survival): 4.1 months
  * OS (overall survival): 13.7 months

2. Middle Section - Shows different patient response groups:
- Separates patients into different categories with survival times
- Shows response rates varying from around 19% to 95%

3. Right Section - SelectPSMA Results:
- Compares patients predicted to respond (51% response rate) vs non-responders (6% response rate)
- Shows the difference in survival times between these groups
- Demonstrates how the AI tool might help predict which patients will benefit most

The different colored bars and numerical values help visualize the differences in outcomes between different patient groups and highlight the potential value of using SelectPSMA for patient selection.

Abstract

[¹⁷⁷Lu]Lu-PSMA-617 was approved by the U.S. Food and Drug Administration for patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC). Since the time of regulatory approval, however, real-world data have been lacking. This study investigated the efficacy, safety, and outcome predictors of [¹⁷⁷Lu]Lu-PSMA-617 at a major U.S. academic center.  

Methods: Patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 at the Johns Hopkins Hospital outside clinical trials were screened for inclusion. Patients who underwent [¹⁷⁷Lu]Lu-PSMA-617 and had available outcome data were included in this study. Outcome data included prostate-specific antigen (PSA) response (≥50% decline), PSA progression-free survival (PFS), and overall survival (OS). Toxicity data were evaluated according to the Common Terminology Criteria for Adverse Events version 5.03. The study tested the association of baseline circulating tumor DNA mutational status in homologous recombination repair, PI3K alteration pathway, and aggressive-variant prostate cancer–associated genes with treatment outcome. Baseline PSMA PET/CT images were analyzed using SelectPSMA, an artificial intelligence algorithm, to predict treatment outcome. Associations with the observed treatment outcome were evaluated.  

Results: All 76 patients with PSMA-positive mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 met the inclusion criteria. A PSA response was achieved in 30 of 74 (41%) patients. The median PSA PFS was 4.1 mo (95% CI, 2.0–6.2 mo), and the median OS was 13.7 mo (95% CI, 11.3–16.1 mo). Anemia of grade 3 or greater, thrombocytopenia, and neutropenia were observed in 9 (12%), 3 (4%), and 1 (1%), respectively, of 76 patients. Transient xerostomia was observed in 23 (28%) patients. The presence of aggressive-variant prostate cancer–associated genes was associated with a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P = 0.040). No other associations were observed between circulating tumor DNA mutational status and treatment outcomes. Eighteen of 71 (25%) patients classified by SelectPSMA as nonresponders had significantly lower rates of PSA response than patients classified as likely responders (6% vs. 51%; P < 0.001), a shorter PSA PFS (median, 1.3 vs. 6.3 mo; P < 0.001), and a shorter OS (median, 6.3 vs. 14.5 mo; P = 0.046).  

Conclusion: [¹⁷⁷Lu]Lu-PSMA-617 offered in a real-world setting after regulatory approval in the United States demonstrated antitumor activity and a favorable toxicity profile. Artificial-intelligence–based analysis of baseline PSMA PET/CT images may improve patient selection. Validation of these findings on larger cohorts is warranted