Phase 3 Study Shows Viability of 177Lu-PSMA-617 for Taxane-Naïve Metastatic Castration-Resistant Prostate Cancer

For taxane-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), results from a multicenter phase 3 randomized trial demonstrate that ¹⁷⁷Lu-PSMA-617 could be a viable alternative to a change of androgen receptor pathway inhibitor (ARPI) therapy.

For the study, recently published in the Lancet, researchers compared intravenous administration of ¹⁷⁷Lu-PSMA-617 (Pluvicto, Novartis) to a change of ARPI therapy (enzalutamide or abiraterone) in 468 taxane-naïve patients with mCRPC. All patients had experienced disease progression with previous ARPI therapy, according to the study. The median age for those receiving ¹⁷⁷Lu-PSMA-617 was 71 and the median age for the ARPI therapy change cohort was 72.

In the primary analysis with the first data cutoff, the researchers found the ¹⁷⁷Lu-PSMA-617 group had a median radiographic progression-free survival (rPFS) of 9.3 months in comparison to 5.55 months for participants in the ARPI therapy change cohort. At the third data cutoff, ¹⁷⁷Lu-PSMA-617 was associated with an 11.6-month median rFPS in contrast to 5.59 months for those who had a change of ARPI therapy.

“Treatment with ¹⁷⁷Lu-PSMA-617 led to a clinically meaningful prolongation of radiographic progression-free survival compared with ARPI change in taxane-naive patients with PSMA-positive metastatic castration-resistant prostate cancer,” noted lead study author Michael J. Morris, M.D., who is affiliated with the Genitourinary Oncology Service at the Memorial Sloan Kettering Cancer Center in New York, N.Y., and colleagues.

At the third data cutoff, the study authors pointed out that 51 percent of the ¹⁷⁷Lu-PSMA-617 cohort had a confirmed prostate-specific antigen (PSA) response (defined in the study as a 50 percent or greater decrease in PSA level), which was three times higher than that reported in the ARPI change cohort (17 percent).

(Editor’s note: For related content on prostate cancer imaging, click here.)

The researchers noted a higher median duration of exposure at the third data cutoff for participants receiving ¹⁷⁷Lu-PSMA-617 (8.41 months) in comparison to those in the ARPI change cohort (6.52 months). However, the study authors also pointed out a lower incidence of grade 3 or higher treatment-emergent adverse effects with ¹⁷⁷Lu-PSMA-617 (36 percent) than those reported in the ARPI change group (48 percent).

The most common adverse events for those in the ¹⁷⁷Lu-PSMA-617 cohort were dry mouth, asthenia, nausea, and anemia, according to the study.

¹⁷⁷Lu-PSMA-617 had a (favorable) safety profile, with a lower incidence of grade 3–4 or serious adverse events despite a longer median duration of exposure than the study ARPI treatment,” noted Morris and colleagues.

(Editor’s note: For related content, see “Could Pluvicto Have a Role in Taxane-Naïve mCRPC?: an Interview with Oliver Sartor, MD,” “Emerging Perspectives on PSMA PET Radiotracers: an Interview with Kenneth J. Pienta, MD,” and “Emerging PSMA Radioligand Therapy Shows Benefits for Metastatic Castration-Resistant Prostate Cancer.”)

In regard to study limitations, the authors acknowledged possible bias with clinical and safety endpoints due to the lack of double blinding. They also conceded the exclusion of patients with known homologous recombination repair (HRR) gene alterations that have been associated with mCRPC.