FDA Expands Indication for Lutetium Lu 177 Vipivotide Tetraxetan in PSMA-Positive mCRPC
Expert Perspectives · Lyn Brook · 2025-03-31
The FDA has announced an expanded indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto®, Novartis). This approval now includes adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have previously undergone androgen receptor pathway inhibitor (ARPI) therapy and are deemed suitable for delaying taxane-based chemotherapy. Previously, it was approved for patients with PSMA-positive mCRPC who had received both ARPI therapy and taxane-based chemotherapy.
Why This Approval Matters
This decision provides a new therapeutic option for patients with advanced prostate cancer, offering a targeted approach to treatment. Selection of patients for lutetium Lu 177 vipivotide tetraxetan therapy should be based on PSMA expression in tumors, as determined by gallium Ga 68 gozetotide (Locametz®, Novartis) or another FDA-approved PSMA positron emission tomography (PET) imaging agent.
Breaking Down the PSMAfore Trial
The expanded approval is supported by efficacy data from the PSMAfore trial (NCT04689828), a multicenter, open-label study that evaluated the efficacy and safety of lutetium Lu 177 vipivotide tetraxetan in 468 patients with PSMA-positive mCRPC. All participants had disease progression on one ARPI and were considered appropriate candidates for delaying taxane-based chemotherapy.
Patients were randomized 1:1 to receive either lutetium Lu 177 vipivotide tetraxetan (7.4 GBq every six weeks for up to six doses) or a change in ARPI therapy. Notably, patients in the ARPI arm who experienced disease progression were allowed to cross over to the experimental therapy.
The primary efficacy end point was radiographic progression-free survival (rPFS), assessed by blinded independent central review. The secondary end point was overall survival (OS).
Results demonstrated a significant improvement in rPFS for patients treated with lutetium Lu 177 vipivotide tetraxetan. The median rPFS was 9.3 months in the lutetium Lu 177 vipivotide tetraxetan arm compared with 5.6 months in the ARPI arm. While the median OS was numerically higher in the lutetium Lu 177 vipivotide tetraxetan arm—24.5 months versus 23.1 months—the difference was not statistically significant.
Importantly, 60% of patients in the ARPI arm (n=141) crossed over to receive lutetium Lu 177 vipivotide tetraxetan after disease progression, underscoring the therapy’s potential benefit in this population.
Managing Adverse Events
The safety profile of lutetium Lu 177 vipivotide tetraxetan was consistent with prior clinical experience. Common adverse events included myelosuppression, renal toxicity, and risks associated with radiation exposure. Healthcare providers should monitor patients closely for these potential complications.
Conclusion
“Lutetium Lu 177 vipivotide tetraxetan prolonged radiographic progression-free survival relative to ARPI change, with a favorable safety profile,” concluded Michael Morris, MD, the Prostate Cancer Section Head in Genitourinary Oncology at Memorial Sloan Kettering Cancer Center, and colleagues, in their published results of the PSMAfore trial. “For patients with PSMA-positive mCRPC who are being considered for a change of ARPI after progression on a previous ARPI, lutetium Lu 177 vipivotide tetraxetan may be an effective treatment alternative.”
Recommended Dosage
The recommended dose of lutetium Lu 177 vipivotide tetraxetan is 7.4 GBq (200 mCi) administered intravenously every six weeks for up to six doses, or until disease progression or unacceptable toxicity occurs.