[177Lu]Lu-PSMA-617 Delays TTW in Patients With Taxane-Naïve mCRPC Over ARPIs

The phase 3 PSMAfore study began in 2021 to compare the prolonged radiographic progression-free survival benefits of [¹⁷⁷Lu]Lu-PSMA-617 (Lu617) against change of androgen receptor pathway inhibitors (ARPIs) in taxane-naïve patients with metastatic castration-resistant prostate cancer (mCRPC).

At the 2024 American Society of Clinical Oncology Annual Meeting, Karim Fizazi, MD, PhD, presented new results of the study’s second interim analysis, including health-related quality of life (HRQOL) and pain outcomes.

A randomized selection of 468 patients with mCRPC was included in the trial. Each patient was an eligible candidate for change of ARPI after progression on 1 prior ARPI and had ≥1 prostate-specific membrane antigen (PSMA)-positive and no exclusionary PSMA-negative metastatic lesions based on [⁶⁸Ga]Ga-PSMA-11 positron emission tomography/computed tomography scan.

Each patient received 6 cycles of open-label Lu617 at 7.4 GBq/6 weeks (n=234) or ARPI change (abiraterone/enzalutamide; n=234). Patients who had confirmed radiographic progression on ARPI change were crossed over to receive Lu617.

The study’s secondary end points included time to worsening (TTW) in self-reported HRQOL (FACT-P, EQ-5D-5L) and pain (BPI-SF), defined as a composite of score worsening (prespecified thresholds), clinical progression (including new anticancer treatment), or death.

The median age of the patient group was 72 years (range, 43-94 years). The median duration of exposure in the Lu617 arm was 8.4 months, and it was 6.5 months in the ARPI change arm. Lu617 was found to delay TTW on the FACT-P, EQ-5D-5L, and BPI-SF scales and subscales versus ARPI change.

Treatment with Lu617 offered a median FACT-P total score of 7.46 (range, 6.08-8.51) over an ARPI change score of 4.27 (range, 3.48-4.53), as well as an EQ-5D-5L utility score of 6.14 (range, 4.70-7.92) and a BPI-SF pain intensity score of 5.03 (range, 4.40-6.87) over ARPI change scores of 3.88 (range, 3.25-4.40) and 3.71 (range, 3.09-4.37), respectively.

Overall, Lu617 provided higher beneficial responses and delayed TTW over ARPI change for the treatment of taxane-naïve PSMA-positive mCRPC.