Lutetium (Lu)-177–PSMA-617 radioligand therapy may offer a statistically significant and clinically meaningful radiographic progression-free survival benefit in patients with taxane-naive metastatic castration-resistant prostate cancer, according to findings presented by Herrmann et al at the 2024 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting (Abstract 241064). The report was also honored as the meeting’s Abstract of the Year.
Background
“Findings from the pivotal phase III VISION trial led to the U.S. Food and Drug Administration (FDA) approval of Lu-177–PSMA-617 for [patients with prostate-specific membrane antigen] (PSMA)-positive [metastatic castration-resistant prostate cancer] previously treated with both an androgen-receptor pathway inhibitor … and taxane-based chemotherapy,” highlighted lead study author Ken Herrmann, MD, Chair of the Department of Nuclear Medicine at University Hospital Essen in Germany. “The current PSMAfore study aims to assess the benefit of Lu-177–PSMA-617 in patients with [metastatic castration-resistant prostate cancer] who have never received taxane-based chemotherapy with the hope of making this promising therapy available to more patients earlier in the course of their treatment journey,” he added.
Study Methods and Results
In the PSMAfore study, the researchers enrolled 468 patients with taxane-naive metastatic castration-resistant prostate cancer who had PSMA-positive disease on gallium-68–PSMA-11 positron-emission tomography/computed tomography and were candidates for an androgen-receptor pathway inhibitor change after one progression on prior androgen-receptor pathway inhibitor therapy. They randomly assigned the patients to receive Lu-177–PSMA-617 or a change in androgen-receptor pathway inhibitor therapy to abiraterone or enzalutamide. The primary endpoint of the study was radiographic progression-free survival, and the secondary endpoint was overall survival. The researchers also assessed prostate-specific antigen (PSA) declines of 50% or more from baseline—known as a PSA50 response—health-related quality of life, safety, time to PSA progression, and objective response rates. They conducted a primary analysis at 7.3 months and a second interim analysis at 15.9 months in both patient groups.
At primary analysis, the patients in the Lu-177–PSMA-617 group experienced a median radiographic progression-free survival of 9.30 months vs 5.55 months among those in the androgen-receptor pathway inhibitor change group (hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.29–0.56). The results were similar at the second interim analysis—in which the researchers demonstrated that compared with those in the androgen-receptor pathway inhibitor group, the patients in the Lu-177–PSMA-617 group experienced a longer median time to worsening in FACT-P total scores (7.46 months vs 4.27 months), higher objective response rates (50.7% vs 14.9%), higher PSA50 responses (57.6% vs 20.4%), and longer median time to PSA progression (10.55 months vs 4.24 months).
Additionally, the researchers found that Lu-177–PSMA-617 was well tolerated and had a manageable safety profile consistent with the safety profile and tolerability observed in the VISION trial. The incidence of grade > 3 adverse events in the second interim analysis were fewer for the patients who received Lu-177–PSMA-617 compared with those who received an androgen-receptor pathway inhibitor change. Among those in the Lu-177–PSMA-617 group, the most common groups of any-grade treatment-emergent adverse events, according to safety topics of interest, were dry mouth and myelosuppression.
Conclusions
“Patients with advanced prostate cancer face an unmet need for treatments that offer clinically meaningful benefits while minimizing impact of severe adverse events. Results from the PSMAfore study suggest that Lu-177–PSMA-617 may have the potential to change the treatment paradigm for patients with advanced prostate cancer in the pretaxane setting,” underscored co–study author Oliver Sartor, MD, Director of Radiopharmaceutical Trials at the Mayo Clinic in Minnesota.
The new findings add to growing evidence that Lu-177–PSMA-617 may be effective and tolerable in patients in the earlier lines of advanced prostate cancer. The researchers plan to submit an application to the FDA for a label expansion for Lu-177–PSMA-617 in the pretaxane setting for the second half of 2024. If approved, these data will be incorporated into the updated product prescribing information, providing earlier access to this therapy.
Disclosure: For full disclosures of the study authors, visit xcdsystem.com.
