Real-world data highlight clinical benefit of 177Lu-PSMA-617 in mCRPC

Real-world data demonstrate the clinical efficacy of the radioligand therapy ¹⁷⁷Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan; Pluvicto) in patients with heavily pretreated metastatic-castration resistant prostate cancer (mCRPC), according to findings from a single-institution retrospective analysis shared at the 2024 Genitourinary Cancers Symposium.¹

Regarding next steps, the authors wrote, “Characterization of response rates within subgroups by prior treatment and disease characteristics are ongoing.”

At a median follow-up of 7.6 months (range, 0.6-14.1), 21% of patients had a PSA90 response, 52% had a PSA50 response, and 61% had a PSA30 response. Twenty-eight percent of patients had an increase or no change in PSA from baseline. Of note, 3 patients with an initial rise in PSA after their first treatment experienced a subsequent decline from their baseline PSA level.

“This data supports the clinical benefit of ¹⁷⁷Lu-PSMA-617 in real-world clinical practice,” the researchers wrote in their poster conclusion.

Overall, the retrospective analysis included the first 100 patients with mCRPC treated with a minimum of 1 cycle of ¹⁷⁷Lu-PSMA-617 at Duke University from June 2022 to August 2023. Of these 100 patients, 98 were evaluable for efficacy. There were 2 patients determined to be ineligible for the analysis because they had received ¹⁷⁷Lu-PSMA-617 on a prior clinical trial.

For the 98 eligible patients, the median age at diagnosis was 61 years (range, 46-89) and the median age at the start of treatment was 72 years (range, 50-93). Over two-thirds (69%) of the patients were white, 28% were Black or African American, 1% were American Indian or Alaskan Native, and 2% preferred not to answer questions about race.

The median baseline PSA level was 25.96 ng/mL (range, 3.87-5030) and the median Gleason score at diagnosis was 8 (range, 6-10). Forty-four percent of patients had de novo metastatic disease. Sites of metastases included bone plus nodal metastases (44%), bone metastases only (19%), nodal metastases only (8%), and liver metastases only (11%). Regarding prior treatment, 47% of patients had at least 2 prior androgen receptor signaling inhibitors, 48% had at least 2 prior taxanes, 42% had 1 prior taxane, and 17% had prior radium-223 (Xofigo).

The primary outcome measure was best PSA response, focusing on a PSA reduction from baseline of 30% (PSA30), 50% (PSA50), or 90% (PSA90) at any time point during treatment.

The researchers noted on their poster that their results are limited by “duration of response and time to follow-up.”

Regarding next steps, the authors wrote, “Characterization of response rates within subgroups by prior treatment and disease characteristics are ongoing.”

FDA approval of ¹⁷⁷Lu-PSMA-617

¹⁷⁷Lu-PSMA-617 is approved by the FDA for the treatment of adult patients with PSMA-positive mCRPC who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy.²

The approval was based on findings from the phase 3 VISION trial (NCT03511664), which showed that adding ¹⁷⁷Lu-PSMA-617 to standard of care significantly improved overall survival and progression-free survival compared with standard of care alone in patients with advanced PSMA-positive mCRPC.³

Reference

1. Maldonado Grijalva V, Wang J, Nedrud M, et al. Real-world clinical outcomes of patients treated with Lu-177-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC): A single-institution experience. J Clin Oncol 42, 2024 (suppl 4; abstr 83) doi: 10.1200/JCO.2024.42.4_suppl.83

2. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. Published online March 23, 2022. Accessed November 29, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer.

3. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. doi: 10.1056/NEJMoa2107322