Rad Onc First to Dose 177Lu in US, Notes Enormity of Recent mCRPC Approval

“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],” Finkelstein said during an interview with CancerNetwork®.

On April 3, 2025, Steven Finkelstein, MD, DABR, FACRO, and his team were the first in the US to administer the recently approved lutetium Lu 177 (177Lu; Pluvicto) to a patient with metastatic castration-resistant prostate cancer (mCRPC).¹ On March 28, 2025, the FDA gave extended approval to 177Lu for patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who have previously been treated with an androgen receptor pathway inhibitor (ARPI) and may be eligible to delay taxane-based chemotherapy. ²

When the approval happened, Finkelstein, national director of Radiation Oncology at US Urology Partners, director of the Center of Advanced Radiation Excellence, and director of Radiation Oncology Research at AMP in Syracuse, NY, noted that he had come to work with this patient as they wanted to be placed on the regimen prior to the FDA approval.

“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],” Finkelstein said during an interview with CancerNetwork®.

The FDA approval was based on results from the phase 3 PSMAfore trial (NCT04689828) assessing 177Lu vs ARPI change.³ A total of 468 patients were randomly assigned 1:1 to either the 177Lu arm (n = 234) or the APRI arm (n = 234). In the 177Lu arm, 7.4 GBq ± 10% was administered once every 6 weeks for 6 cycles. Abiraterone (Zytiga) or enzalutamide (Xtandi) were given in the ARPI change group, and patients could cross over once eligibility criteria were met.

Overall, 3 data cutoffs occurred, and at the last one, 57% of patients in the ARPI group had crossed over to the 177Lu group. Of note 78% of patients had radiographic progression-free survival (rPFS) confirmed by blinded independent central review.

The median rPFS was 9.30 months (95% CI, 6.77-not estimable) in the 177Lu arm vs 5.55 months (95% CI, 4.04-5.95) in the APRI change arm (HR, 0.41; 95% CI, 0.29-0.56; P <.0001). The median follow-up for all randomly allocated patients had a rPFS of 3.71 months in the 177Lu arm with a median number of 3 cycles for those who received 1 dose and 2.35 months in the APRI change arm.

During the third data cutoff, the median rPFS was 11.60 months (95% CI, 9.30-14.19) in the 177Lu arm and 5.59 months (95% CI, 4.21-5.95) in the APRI change arm. The median follow-up was 8.77 months and 4.27 months respectively.

Finkelstein noted during the interview, that to receive the treatment and administer it, the process was fairly easy.

“The dose got to us within 3 business days, and then we were able to dose [the patient] at a convenient time for the patient on the sixth day, and again, the patient was ecstatic that he could have availability for a potentially life-saving therapy,” he said.

Treatment-related adverse effects (TRAEs) of grade 3 or higher were noted in 36% of patients in the 177Lu arm and 48% in the ARPI change group. TRAEs that were considered treatment-related by the investigator were noted in 12% of patients in the 177Lu group and 13% in the APRI change group.

The most common grade 3 or higher TRAEs were anemia (6% vs 7%), dry mouth (1% vs 0%), asthenia (1% vs 3%), and back pain (1% vs 3%) between the 177Lu and ARPI change arms, respectively. There were no TRAEs leading to death in the 177Lu arm, but 1 patient died in the ARPI change arm.

When asked how the patient fared against the AEs observed in the trial, Finkelstein highlighted, “We’ve been in contact with the patient, and the patient has not experienced any adverse effects and has had a favorable safety profile. The findings from the PSMAfore study that led to the approval demonstrated a consistent and favorable safety profile, with the most frequently reported all-grade adverse effects for [177Lu] being primarily grade 1/2 events.”

Overall, Finkelstein discussed that giving 177Lu is a multidisciplinary team approach. He needs to work with and coordinate with urologists, medical oncologists, and nuclear medicine physicians. When they come together with the “team sport” [mentality], the best outcomes for the patient will be achieved.

References

1. CNY man is first patient in US to receive new prostate cancer treatment in pre-chemotherapy setting. News release. LocalSYR.com. https://tinyurl.com/mscphtyj
2. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. News release. FDA. March 28, 2025. Accessed March 28, 2025. https://tinyurl.com/y77tmenc
3. 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