How will PLUDO, PSMAfore, SPLASH, and ECLIPSE Impact Prostate Cancer Management?

Area of Science:

• Oncology
• Nuclear Medicine
• Radiopharmaceutical Therapy

Background:

• Prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is approved for metastatic castration-resistant prostate cancer (mCRPC).
• The VISION trial established ¹⁷⁷Lu-PSMA-617 as a standard of care post-androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy.
• Recent trials investigate PSMA-RLT in earlier mCRPC settings.

Purpose of the Study:

• To review recent phase 3 trial results (PSMAfore, SPLASH, ECLIPSE) on PSMA-RLT in mCRPC.
• To discuss the impact of these findings on mCRPC treatment sequencing.
• To evaluate PSMA-RLT as an option for chemotherapy-naive patients.

Main Methods:

• Review of published and presented results from three phase 3 trials (PSMAfore, SPLASH, ECLIPSE).
• Inclusion of data from select randomized phase 2 trials.
• Analysis of progression-free survival (PFS) and overall survival (OS) data.

Main Results:

• PSMA-RLT demonstrated delayed PFS compared to ARPI in post-ARPI, chemotherapy-naive mCRPC patients.
• ¹⁷⁷Lu-PSMA-617 showed prolonged OS and PFS in previously treated mCRPC patients (VISION trial).
• Emerging data supports PSMA-RLT's efficacy in earlier lines of mCRPC treatment.

Conclusions:

• PSMA-RLT is an effective treatment for mCRPC, both post-chemotherapy and in earlier settings.
• Optimal sequencing of PSMA-RLT within mCRPC management requires further investigation.
• PSMA-RLT offers a new therapeutic avenue for patients ineligible for chemotherapy.