As reported in The Lancet Oncology by Michael S. Hofman, MBBS, and colleagues, the Australian phase II TheraP trial has shown similar overall survival with lutetium-177–labeled PSMA-617 (LuPSMA; lutetium Lu 177 vipivotide tetraxetan) vs cabazitaxel in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer whose disease progressed after treatment with docetaxel.
The primary analysis from the study showed improved prostate-specific antigen responses with LuPSMA vs cabazitaxel.
Michael S. Hofman, MBBS
Study Details
The open-label multicenter trial included 200 eligible patients who had positron-emission tomography (PET) imaging with gallium-68–PSMA-11 (Ga-68–PSMA-11) and 2 fluorine-18–fluorodeoxyglucose (2–F-18 FDG) showing PSMA-positive disease. They were randomly assigned between February 2018 and September 2019 to receive LuPSMA (n = 99) or cabazitaxel (n = 101). LuPSMA was given every 6 weeks for a maximum of six cycles; treatment started at 8.5 GBq and decreased by 0.5 GBq to 6.0 GBq for the sixth cycle. Cabazitaxel was given at 20 mg/m² every 3 weeks for a maximum of 10 cycles. Overall survival was analyzed by intention-to-treat and summarized as restricted mean survival time (RMST) to account for nonproportional hazards, with a 36-month restriction time corresponding to median follow-up.
Key Findings
After completing study treatment, 20 patients (20%) in the cabazitaxel group and 32 (32%) in the LuPSMA group subsequently received the alternative 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 patients (69%) in the cabazitaxel group.
RMST was 19.1 months (95% confidence interval [CI] = 16.9–21.4 months) in the LuPSMA 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).
Among 291 patients registered after initial eligibility screening, 80 (27%) were excluded from the study after Ga-68–PSMA-11 and 2–F-18 FDG PET imaging showed low PSMA expression or 2–F-18 FDG–discordant disease. Among 61 of these patients with available follow-up, RMST was 11.0 months (95% CI = 9.0–13.1 months).
No additional safety signals were identified with the longer follow-up.
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, Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded 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.
