Emerging PSMA Radioligand Therapy Shows Benefits for Metastatic Castration-Resistant Prostate Cancer
The PSMA-targeted modality 177Lu-PNT2002 improved radiographic progression-free survival by 29 percent in patients with mCRPC in comparison to ARPI therapy, according to new phase 3 trial data presented at the ESMO Congress in Spain.
Emerging research presented at the European Society of Medical Oncology (ESMO) Congress suggests that the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy 177Lu-PNT2002 offers significant advantages over androgen-receptor pathway inhibitor (ARPI) treatment of PSMA-positive patients with metastatic castration-resistant prostate cancer (mCRPC).
In the SPLASH phase 3 randomized trial, researchers compared the administration of 177Lu-PNT2002 (6.8 GBq every eight weeks for up to four treatment cycles) to ARPI therapies (abiraterone and enzalutamide) in 412 patients with mCRPC.1
The researchers found that 177Lu-PNT2002 (Lantheus) bolstered radiographic progression-free survival (rPFS) by 29 percent and led to a 3.5 month increase in median rPFS (9.5 months vs. 6.5 months) in contrast to ARPI therapy.1,2
The use of the radioligand therapy 177Lu-PNT2002 was also associated with a longer median duration of response (9.4 months vs. 7.3 months), more than double the PSA50 response rate (35.7 percent vs. 14.6 percent) and longer median biochemical progression-free survival (seven months vs. 3.9 months) in comparison to ARPI modalities, according to the study authors.2
In recent phase 3 trial research presented at the ESMO Congress 2024, researchers found that the PSMA-targeted radioligand 177Lu-PNT2002 offered significantly improved median radiographic progression-free survival (rPFS), biochemical progression-free survival (bPFS) and treatment duration response in comparison to androgen-receptor pathway inhibitor (ARPI) treatment of PSMA-positive patients with metastatic castration-resistant prostate cancer (mCRPC).
“These initial data underscore the importance of PSMA-targeted RLTs, including 177Lu-PNT2002, as potential treatment options for patients who have limited choices after progressing on ARPI therapy,”noted Oliver Sartor, M.D., the director of radiopharmaceutical trials and a professor of medical oncology at the Mayo Clinic in Rochester, Minnesota.
(Editor's note: For related content on imaging for prostate cancer, click here.)
The researchers also pointed out that 177Lu-PNT2002 had lower safety risks than ARPI therapy. Specifically, patients in the 177Lu-PNT2002 cohort had a lower rate of treatment-related serious adverse events (AEs) (2.2 percent vs. 3.8 percent). The study authors said those who had 177Lu-PNT2002 had a greater than threefold lower rate of halted or reduced treatment due to treatment-emergent adverse events (TEAEs) in comparison to patients who had ARPI therapy (3 percent vs. 11.5 percent).1,2
References
1. Lantheus. Lantheus presents results from the primary analysis of phase 3 pivotal SPLASH trial in PSMA-positive metastatic castration-resistant prostate cancer during ESMO Congress 2024. Available at: https://investor.lantheus.com/news-releases/news-release-details/lantheus-presents-results-primary-analysis-phase-3-pivotal . Published September 15, 2024. Accessed September 16, 2024.
2. Sartor O, Jiang DM, Smoragiewicz M, et al. Efficacy of 177LU-PNT2002 in PSMA-positive mCRPC following progression on an androgen-receptor pathway inhibitor (ARPI) (SPLASH). Presented at the European Society for Medical Oncology (ESMO) Congress September 13-17, 2024, Barcelona, Spain. Available at: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/session/list? . Accessed September 16, 2024.
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