FDA Expands Indication for Lutetium-177 PSMA-617 in PSMA-Positive mCRPC

US FDA

• The FDA has expanded the indication for lutetium-177 (¹⁷⁷Lu) vipivotide tetraxetan (¹⁷⁷Lu PSMA-617; Pluvicto).
• The approval now includes adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.
• The PSMAfore (NCT04689828) study evaluated the agent in patients with PSMA-positive mCRPC.

The FDA has expanded the indication for ¹⁷⁷Lu PSMA-617 to include adult patients with PSMA-positive mCRPC who have progressed after ARPI therapy and are considered appropriate candidates for delaying taxane-based chemotherapy.¹

According to a press release from the FDA, patient selection should be guided by PSMA-PET imaging using Ga 68 gozetotide (Locametz) or another approved PSMA-PET tracer.

The approval was based on findings from the PSMAfore trial (NCT04689828), a randomized, open-label, multicenter phase 3 study of 468 patients with PSMA-positive mCRPC who had progressed on 1 prior ARPI and were deemed suitable for deferred taxane therapy. Patients were randomly assigned 1:1 to receive either ¹⁷⁷Lu PSMA-617 at a dose of 7.4 GBq every 6 weeks for up to 6 cycles or a change in ARPI, with crossover permitted upon progression.

Two prostate cancer cells in the final stage of cell division: ©PRB ARTS - stock.adobe.com

The primary end point of the study was radiographic progression-free survival (rPFS) by blinded independent central review. The trial demonstrated a median rPFS of 9.3 months (95% CI, 7-NE) with ¹⁷⁷Lu PSMA-617 vs 5.6 months (95% CI, 4-6) with ARPI switch (HR 0.41; 95% CI, 0.29-0.56; P <.0001).

Looking at interim overall survival (OS) data, a numerical but non-significant improvement was seen, with a median OS of 24.5 months (95% CI, 19.5-28.9) for ¹⁷⁷Lu PSMA-617 vs 23.1 months (95% CI, 19.6-25.5) for ARPI switch (HR 0.91; 95% CI, 0.72-1.14), though 60% of patients in the ARPI arm crossed over to ¹⁷⁷Lu PSMA-617 upon progression.

The safety profile of ¹⁷⁷Lu PSMA-617 was consistent with prior findings, including risks of radiation exposure, myelosuppression, and renal toxicity.

The recommended dose remains 7.4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses, continued until disease progression or unacceptable toxicity.

The FDA was first granted approval to ¹⁷⁷Lu-PSMA-617 for the treatment of patients with mCRPC in the post androgen receptor pathway inhibition, post-taxane-based chemotherapy setting in March 2022.²

References

1. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. News release. FDA. March 28, 2025. Accessed March 28, 2025. https://tinyurl.com/3zn6myku

2. Novartis PluvictoTM approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. News release. Novartis. March 23, 2022. Accessed March 28, 2025. https://bit.ly/3iw9bab