177Lu-PSMA-617 (LuPSMA) was a suitable option for men with metastatic castration-resistant prostate cancer (mCRPC) after progressing on prior docetaxel, according to results from the TheraP ANZUP 1603 trial (Abstract 5000).
Previous research has shown that men with mCRPC who progressed after docetaxel randomly assigned to LuPSMA had significant improvement in prostate-specific antigen (PSA) response rate, RECIST response rate, and progression-free survival compared with cabazitaxel.
Michael S. Hofman, FRACP, MBBS, of Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, presented results of the secondary overall survival endpoint at the 2022 ASCO Annual Meeting.
With a median follow-up of 36 months, overall survival was similar in patients assigned to LuPSMA compared with cabazitaxel (restricted mean survival time to 36 months was 19.1 vs. 19.6 months). The hazard ratio (HR) was 0.97 (95% CI, 0.70-1.40; P=.99).
The study included 291 patients that had progressed after docetaxel. Men had to have PET imaging with 68Ga-PSMA-11 that showed high PSMA-expression (at least one site with SUVmax≥20), and 18F-FDG demonstrating no sites of disease of FDG-positive and PSMA-negative. Two-hundred eligible patients were then randomly assigned to treatment with LuPSMA or cabazitaxel.
Dr. Hofman noted that most of the men sought off trial treatment with LuPSMA, which was available in Australia at the time.
“The primary analysis is intention-to-treat in all these patients assigned cabazitaxel; even if they had LuPSMA [post-protocol], they are assessed as having cabazitaxel,” Dr. Hofman said. He noted that 20% of patients assigned to cabazitaxel had LuPSMA post-protocol and 21% had further cabazitaxel.
As part of this analysis, the researchers reanalyzed progression-free survival, which remained strongly in favor of LuPSMA (HR=0.62; 95% CI, 0.45-0.85; P=.0028).
No additional safety signals were reported related to LuPSMA in this longer follow-up.
The clinical implications of these results are that LuPSMA had similar overall survival to cabazitaxel, a proven life-prolonging therapy but with fewer adverse events and better patient-reported outcomes.
Dr. Hofman also discussed patient selection. Earlier this year, he and his colleagues presented data that PSMA was a predictive biomarker. In this analysis, they found that the odds of PSA response were higher in all participants assigned LuPSMA compared with cabazitaxel, but were almost six times higher with an SUVmean greater than 10 (odds ratio 2.2 vs. 12.2; P=03)
“If you have very high PSMA expression we think these are patients that ought to be prioritized to access LuPSMA therapy,” Dr. Hofman said.
