PSMA Tandem Treatment Offers Benefit for Patients With mCRPC

A phase 3, single-center, prospective, 2-arm controlled trial presented at the 2024 Society of Nuclear Medicine and Molecular Imaging Annual Meeting offers the first randomized evidence of the benefit of prostate-specific membrane antigen (PSMA) radiolabeled tandem therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

Fuad Novruzov, MD, PhD, of the Azerbaijan National Centre of Oncology, and colleagues enrolled 93 patients with advanced-stage mCRPC who were resistant to androgen deprivation therapy (eg, enzalutamide or abiraterone acetate). Patients were randomized to receive a combination of 225-Actinium/177-Lutetium–labeled PSMA for 110 cycles (PSMA tandem treatment; n=50) or standard of care with docetaxel for 73 cycles (n=43).

Researchers assessed for progression-free survival (PFS), and serial prostate-specific antigen (PSA) measurements at 3 months were obtained for response assessment. Adverse events were also monitored.

Dr. Novruzov and colleagues noted that PSA at 3 months had declined in 73 of 110 (66%) cycles compared with 52 of 73 (71%), respectively (P=.285; not statistically significant). PSA at 3 months had increased in 27 of 110 (24%) cycles compared with 21 of 73 (29%), respectively (P=.005; statistically significant).

As for PFS results, researchers reported a median of 3.8 months versus 1.1 months, respectively, in the PSMA tandem versus standard-of-care arms (P=.001). When a PSA decline of <50% was observed, the PFS was 2.5 months versus 2.6 months, respectively (P=.007). When a PSA decline of ≥50% was observed, the PFS was 10.5 months versus 1.8 months, respectively (P=.001).

The PFS at 100 days was 30% compared with 5%, respectively (P=.001).

In the PSMA tandem arm, no severe hematologic toxicity or nephrotoxicity was noted. The most common toxicity reported was grade 1/2 xerostomia (36%).

“Combining alpha (225Ac) and beta (177Lu) radionuclides minimized adverse effects while preserving treatment efficacy [in patients with mCRPC],” study authors concluded. “PSMA radiolabeled therapy opens doors to a brighter future for patients, promising to significantly extend the boundaries of disease progression delay.”