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Review on the Increasing Role for PSMA-Based Radioligand Therapy in Prostate Cancer.

Finn Edler von Eyben1, Irene Virgolini2, Richard Baum3

  • 1Center of Tobacco Control, 5230 Odense, Denmark.

Cancers
|July 27, 2024
PubMed
Summary

Radioligand therapy (RLT) with 177Lu-PSMA-617 improves outcomes for prostate cancer (PCa) patients. Early use and combination therapies enhance progression-free survival in metastatic castration-resistant PCa.

Keywords:
combination therapynuclear medicineprostate neoplasmprostate-specific membrane antigenrandomized controlled trials

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Area of Science:

  • Oncology
  • Nuclear Medicine
  • Radiopharmaceutical Therapy

Background:

  • Two randomized controlled trials (RCTs) in 2021, TheraP and VISION, established 177Lu-PSMA-617 monotherapy's efficacy in reducing prostate-specific antigen (PSA) levels compared to third-line treatments.
  • High-risk prostate cancer (PCa) presents ongoing treatment challenges, necessitating evaluation of novel therapeutic strategies.

Purpose of the Study:

  • To review recent randomized controlled trials (RCTs) evaluating the role of radioligand therapy (RLT) in managing high-risk prostate cancer (PCa).
  • To assess the efficacy of 177Lu-PSMA-617 in various treatment settings, including first-line and second-line therapies for metastatic castration-resistant prostate cancer (mCRPC).

Main Methods:

  • Systematic review of four past and present RCTs involving a total of 1081 patients with prostate cancer (PCa).
  • Analysis of the ENZA-p trial, investigating first-line treatment with enzalutamide (ENZA) combined with 177Lu-PSMA-617 versus ENZA monotherapy.
  • Evaluation of the PSMAfore and SPLASH trials, examining 177Lu-PSMA-617 as a second-line treatment for mCRPC compared to androgen receptor pathway inhibitors.

Main Results:

  • The ENZA-p trial demonstrated longer progression-free survival (PFS) with the combination of enzalutamide (ENZA) and 177Lu-PSMA-617 compared to ENZA monotherapy in first-line treatment for mCRPC.
  • The PSMAfore and SPLASH trials indicated that 177Lu-PSMA-617 as second-line treatment for mCRPC significantly improved PFS over androgen receptor pathway inhibitors (combined p value < 6.9 × 10-6).
  • Overall, these RCTs support the effectiveness of 177Lu-PSMA-617 in improving outcomes for patients with advanced prostate cancer.

Conclusions:

  • Patients with prostate cancer (PCa) benefit from early administration of prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT).
  • Incorporating PSMA-RLT into combination therapies can further enhance treatment efficacy for PCa.
  • The findings support the expanded use of PSMA-RLT in the management of prostate cancer, particularly in earlier treatment lines and combination regimens.