The FDA has expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to include adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibitor therapy and are considered appropriate to delay taxane-based chemotherapy.1.2
In March 2022, the radioligand therapy was approved by the FDA for the treatment of adult patients with PSMA-positive metastatic castration-resistant prostate cancer who have previously received other anticancer therapies, such as AR pathway inhibition and taxane-based chemotherapy.3
Approval of the expanded indication was supported by data from the phase 3 PSMAfore trial (NCT04689828), which showed that in patients with PSMA-positive mCRPC who received prior treatment with an AR patheway inhibitor and were cosidered appropriate for delayed taxane-based chemotherapy, lutetium Lu 177 vipivotide tetraxetan (n = 234) generated a radiographic progression-free survival (rPFS) of 9.3 months (95% CI, 7-not estimable) vs 5.6 months (95% CI, 4-6) for a switched AR pathway inhibitor (n = 234; HR 0.41; 95% CI, 0.29-0.56; P < .0001).1,4
“The earlier indication for [lutetium Lu 177 vipivotide tetraxetan] could really change our treatment paradigms for patients with mCRPC. It offers a targeted therapy that better delays disease progression compared [with] a second AR pathway inhibitor,” Michael Morris, MD, head of the Prostate Cancer Section in GU Oncology at Memorial Sloan Kettering Cancer Center, and the principal Investigator of PSMAfore, stated in a news release.2 “This approval is a significant step forward and should open the doorway to a therapy that has clear clinical advantages for the patient with mCRPC who has progressed on one AR pathway inhibitor and has not received chemotherapy.”
The randomized, controlled, open-label, multicenter PSMAfore study enrolled 468 patients with PSMA-positive mCRPC who experienced disease progression on a prior AR pathway inhibitor.1 Patients were required to be considered appropriate candidates to delay taxane-based chemotherapy, per investigator discretion.
Investigators randomly assigned patients 1:1 to receive lutetium Lu 177 vipivotide tetraxetan at 7.4 GBq (200 mCi) once every 6 weeks for a total of 6 doses; or a change in AR pathway inhibitor. Patients in the control arm who experienced were allowed to cross over to receive lutetium Lu 177 vipivotide tetraxetan after disease progression.
The trial's primary end point was rPFS per blinded independent central review. Secondary end points comprised overall survival (OS) and safety.
Additional data showed that there was no statistically significant difference in OS. The median OS was 24.5 months (95% CI, 19.5-28.9) for lutetium Lu 177 vipivotide tetraxetan compared with 23.1 months (95% CI, 19.6-25.5) for an AR pathway inhibitor (HR, 0.91; 95% CI, 0.72-1.14). Notably, 60% of patients randomly assigned to the control arm crossed over to receive lutetium Lu 177 vipivotide tetraxetan following disease progression.
References
FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication
FDA approves Novartis radioligand therapy Pluvicto for earlier use before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer. News release. Novartis. March 28, 2025. Accessed March 28, 2025. https://www.novartis.com/news/media-releases/fda-approves-novartis-radioligand-therapy-pluvicto-earlier-use-chemotherapy-psma-positive-metastatic-castration-resistant-prostate-cancer
FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. March 23, 2022. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer?utm\_medium=email&utm\_source=govdelivery
Morris MJ, Castellano D, Herrmann K, et al. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024;404(10459):1227-1239. doi:10.1016/S0140-6736(24)01653-2