Michael S. Hofman, MBBS
As reported in The Lancet Oncology by Michael S. Hofman, MBBS, and colleagues, overall survival results from the Australian phase II TheraP trial showed no difference with lutetium-177–labeled PSMA-617 (LuPSMA) vs cabazitaxel in patients with metastatic castration-resistant prostate cancer and disease progression after treatment with docetaxel.
The initial report from the trial showed improved prostate-specific antigen response rate (66% vs 37%), objective response rate (49% vs 24%), and progression-free survival (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.46–0.86) with LuPSMA vs cabazitaxel.
Study Details
In the open-label multicenter trial, 200 patients enrolled between February 2018 and September 2019 were randomly assigned to receive either:
- LuPSMA every 6 weeks for a maximum of six cycles, starting at 8.5 GBq and decreasing by 0.5 GBq to 6.0 GBq for the sixth cycle (n = 99)
- Cabazitaxel at 20 mg/m² every 3 weeks for a maximum of 10 cycles.
Patients had positron-emission tomography (PET) imaging with gallium-68–PSMA-11 and 2–fluorine-18 fluoro-2-deoxy-D-glucose (2–F-18 FDG) showing prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2–F-18 FDG–positive and PSMA-negative findings. Previous treatment with an androgen receptor pathway inhibitor was allowed. Overall survival, a secondary endpoint, was analyzed as restricted mean survival time, with a 36-month restriction time corresponding to median follow-up.
Key Findings
After completing study treatment, 32 patients (32%) in the LuPSMA group and 20 (20%) in the cabazitaxel group received treatment with the alternate study regimen. After a median follow-up of 35.7 months (interquartile range = 31.1–39.2 months), death had occurred in 77 patients (78%) in the LuPSMA group and in 70 (69%) in the cabazitaxel group. Restricted mean survival time was 19.1 months (95% CI = 16.9–21.4 months) in the LuPSMA group vs 19.6 months (95% CI = 17.4–21.8 months) in the cabazitaxel group (difference = –0.5 months, 95% CI = –3.7 to 2.7 months, P = .77).
Analysis of 61 patients (of a total of 80) who were excluded from the study due to ineligibility on gallium-68–PSMA-11 and 2–F-18 FDG PET in screening, restricted mean survival time was 11.0 months (95% CI = 9.0–13.1 months). The most common treatments among these 61 patients were cabazitaxel (48%) and enzalutamide (7%); LuPSMA was given to 5%.
No additional safety signals were identified with longer follow-up in the current analysis.
The investigators concluded: “These results support the use of [LuPSMA] as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomized groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or [2–F-18 FDG]-discordant disease.”
Dr. Hofman, of the Prostate Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funding by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), and others. For full disclosures of the study authors, visit thelancet.com.
