177Lu Marks Practice-Changing Approval in Metastatic CRPC

A significant milestone for the metastatic castration-resistant prostate cancer (mCRPC) space was reached with the expanded FDA approval of lutetium Lu 177 (177Lu; Pluvicto) in the chemotherapy-naive setting.¹ This decision, driven by the results of the pivotal phase 3 PSMAfore trial (NCT04689828), marked a paradigm shift in the treatment algorithm for patients with prostate-specific membrane antigen (PSMA)–positive mCRPC who have previously received an androgen receptor pathway inhibitor (ARPI) and are not yet candidates for taxane-based chemotherapy.²

This approval was particularly noteworthy as it expanded the utility of 177Lu to an earlier line of therapy, potentially delaying the need for cytotoxic chemotherapy and its associated adverse effects.

Steven Finkelstein, MD, DABR, FACRO, national director of Radiation Oncology at US Urology Partners, director of the Center of Advanced Radiation Excellence, and director of Radiation Oncology Research at Associated Medical Professionals in Syracuse, NY, shared his firsthand account of treating the first patient in the US with 177Lu following the FDA’s decision.³ He also recounted the trial results leading to the approval and how the agent benefited his patient.

Transcript:

On March 28, 2025, the FDA approved [177Lu] in the chemotherapy-naive [mCRPC] space. This was because of the seminal phase 3 PSMAfore trial. In this study, [177Lu] reduced the risk of radiographic progression or death by 59% with an HR of 0.41 [95% CI, 0.29-0.56; P <.0001] compared with a change in an ARPI in patients with PSMA-positive, [mCRPC] after treatment with ARPI therapy. In the updated exploratory analysis, [177Lu] more than doubled the median radiographic progression-free survival at 11.6 months as compared with [5.59] months. With this, again, the FDA approved [lutetium Lu 177] in the chemotherapy-naive [mCRPC] space, allowing patients like mine to finally get [177Lu] prior to chemotherapy. A patient of mine had been waiting patiently, hoping that this approval would happen so that he could receive on-label, commercially available radiopharmaceuticals.

This was a patient who had seen multiple therapies. He was reticent about starting chemotherapy, although he had a medical oncologist who suggested not to get chemotherapy and referred the patient to me previously so that he could be considered for [177Lu]. When I saw him, I told him, unfortunately, it wasn’t available. The FDA had not yet approved it. Then, on March 28, 2025, with the FDA approval, we called the patient and said, “This is rational and reasonable, and we’re able to order the dose within about 30 minutes after the FDA approval.” That dose came a few days later, and we were able to dose the patient within 6 days of the FDA approval. As you can imagine, he was quite excited, and again, was pleased that he could be the first person to receive [177Lu] in the chemotherapy-naïve [mCRPC] space as the first on-label commercial patient.

References

1. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. News release. FDA. March 28, 2025. Accessed April 10, 2025. https://tinyurl.com/y77tmenc
2. 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. Published correction appears in Lancet. 2025 Dec 21;404(10471):2542. doi: 10.1016/S0140-6736(24)02716-8
3. Broddus K. CNY man is first patient in US to receive new prostate cancer treatment in pre-chemotherapy setting. News release. April 3, 2025. Accessed April 10, 2025. LocalSYR.com. https://tinyurl.com/mscphtyj