¹⁷⁷Lu-PSMA-617 Prolongs rPFS in Taxane-Naïve PSMA+ mCRPC

Treatment with ¹⁷⁷Lu-PSMA-617 is more effective than a change in androgen receptor pathway inhibitor (ARPI) therapy for taxane-naïve patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC), according to data presented at the ESMO Congress 2023.

Researchers found that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival (rPFS) and response rates, when compared to a change in ARPI therapy. ¹⁷⁷Lu-PSMA-617 did not improve overall survival (OS), however.

This trial, PSMAfore (ClinicalTrials.gov Identifier: NCT04689828), enrolled adults with progressive mCRPC, at least 1 PSMA-positive metastatic legion, and no exclusionary PSMA-negative lesions. Patients were required to have disease progression on a prior second-generation ARPI and to be taxane-naïve or have received (neo)adjuvant taxane therapy more than 12 months before randomization.

A total of 468 patients were randomly assigned to receive ¹⁷⁷Lu-PSMA-617 (n=234) once every 6 weeks for 6 cycles or to have a change in ARPI therapy (n=234; abiraterone or enzalutamide). Baseline characteristics were generally well balanced between the treatment arms.

Patients in the ARPI-change arm were allowed to cross over to the ¹⁷⁷Lu-PSMA-617 arm upon radiographic progression by independent review. Ultimately, 84.2% of patients who discontinued ARPI therapy due to progression crossed over to the ¹⁷⁷Lu-PSMA-617 arm (123/146).

Efficacy and Safety Results

The researchers found that ¹⁷⁷Lu-PSMA-617 more than doubled rPFS. The median rPFS was 12.02 months with ¹⁷⁷Lu-PSMA-617 and 5.59 months with a change in ARPI therapy (hazard ratio [HR], 0.43; 95% CI, 0.33-0.54).

The overall radiographic response rate was 50.7% in the ¹⁷⁷Lu-PSMA-617 arm and 14.9% in the ARPI-change arm. The complete response rate was 21.1% and 2.7%, respectively. The median duration of response was 13.63 months and 10.05 months, respectively.

The proportion of patients with at least a 50% decrease in prostate-specific antigen level from baseline was 57.6% in the ¹⁷⁷Lu-PSMA-617 arm and 20.4% in the ARPI-change arm.

In an intent-to-treat analysis, there was no significant difference in OS between the treatment arms. The median OS was 19.25 months in the ¹⁷⁷Lu-PSMA-617 arm and 19.71 months in the ARPI-change arm (HR, 1.16; 95% CI, 0.83-1.64).

In a crossover-adjusted analysis, the median OS was 19.25 months in the ¹⁷⁷Lu-PSMA-617 arm and 19.55 months in the ARPI-change arm (HR, 0.80; 95% CI, 0.48-1.33).

Symptomatic skeletal events were less likely in the ¹⁷⁷Lu-PSMA-617 arm than in the ARPI-change arm (9.0% and 23.1%, respectively).

The rate of treatment-emergent adverse events (TEAEs) was 98.2% in the ¹⁷⁷Lu-PSMA-617 arm and 96.1% in the ARPI-change arm. The rate of grade 3/4 TEAEs was 33.9% and 43.1%, respectively. There were 4 fatal TEAEs in the ¹⁷⁷Lu-PSMA-617 arm and 5 in the ARPI-change arm.

The most common TEAEs in the ¹⁷⁷Lu-PSMA-617 arm were dry mouth (57.3%), asthenia (31.7%), nausea (31.3%) and anemia (24.2%). The most common TEAEs in the ARPI-change arm were asthenia (28.9%), fatigue (25.4%), and arthralgia (20.7%).

Disclosures: This research was supported by Novartis. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Sartor O, Castellano Guana DE, Herrmann K, et al. Phase III trial of [177Lu]Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer (PSMAfore). Presented at ESMO Congress 2023. Oct. 20-24, 2023. Madrid, Spain. Abstract LBA13.

This article originally appeared on Cancer Therapy Advisor