Dr Garcia on the Effect of the Expanded Approval of Lutetium Lu 177 Vipivotide Tetraxetan in in PSMA+ mCRPC

[With this expanded approval], our patients can start using [lutetium Lu 177 vipivotide tetraxetan] even earlier. [It is] still restricted to a castration-resistance setting, but they now don't have to go through chemotherapy first to get it.”

Jorge A. Garcia, MD, chair of the Department of Solid Tumor Oncology at the Cleveland Clinic Taussig Cancer Institute, discussed the clinical impact of the FDA’s expanded approval of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) for the treatment of patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC).

On March 28, 2025, the FDA updated the indication for lutetium Lu 177 vipivotide tetraxetan to include adult patients with PSMA-positive mCRPC who have received prior androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy. The agent was initially approved by the regulatory agency in March 2022, but the original indication required patients with mCRPC to receive prior treatment with an ARPI and taxane-based chemotherapy.

The expanded indication allows use of lutetium Lu 177 vipivotide tetraxetan in a pre-chemotherapy setting and builds on the agent’s initial approval, which was based on findings from the phase 3 VISION trial (NCT03511664). With the new approval, patients may now receive the radioligand therapy following progression on an ARPI alone, provided they have PSMA-positive disease confirmed by PET imaging.

Garcia noted that this label revision addresses a clinical disconnect between molecular imaging findings and treatment access. He emphasized that PSMA expression is a functional biomarker, and patients with PSMA-positive scans should be eligible for PSMA-targeted therapies, regardless of prior chemotherapy exposure. The ability to initiate lutetium Lu 177 vipivotide tetraxetan earlier in the disease course reflects a biomarker-driven approach to treatment sequencing.

Previously, many patients eligible for lutetium Lu 177 vipivotide tetraxetan under the original label had heavily pretreated, late-stage disease, and they often exhibited cumulative toxicities and declining performance status, Garcia said. The revised indication now provides a therapeutic option for patients who have received androgen deprivation therapy and a next-generation ARPI but are not yet ready or eligible for chemotherapy.

Garcia explained that this change offers clinical benefit by preserving quality of life and deferring taxane-associated toxicities. It also reflects a broader shift toward the earlier integration of radioligand therapy in the treatment of mCRPC, he concluded.