In the Australian phase II trial TheraP reported in The Lancet, Michael S. Hofman, FRACP, MBBS, and colleagues found that Lutetium-177–labeled PSMA-617 (LuPSMA) treatment was associated with a higher prostate-specific antigen (PSA) response rate and fewer severe adverse events vs cabazitaxel in patients with metastatic castration-resistant prostate cancer.
LuPSMA is a radiolabeled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA).
Michael S. Hofman, FRACP, MBBS
Study Details
In the open-label multicenter trial, 200 men with positron-emission tomography/computed tomography (PET/CT)-confirmed PSMA-positive disease were randomly assigned between February 2018 and September 2019 to receive LuPSMA at 6.0 to 8.5 GBq intravenously every 6 weeks for up to six cycles (n =99) or cabazitaxel at 20 mg/m² intravenously every 3 weeks for up to 10 cycles (n = 101). Patients underwent gallium-68 PSMA-11 and fluorodeoxyglucose F-18 (FDG) PET/CT, with PET eligibility criteria consisting of PSMA-positive disease with no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings.
Among the randomly assigned patients, study treatment was received by 98 (99%) of those in the LuPSMA group vs 85 (84%) of those in the cabazitaxel group. The primary endpoint was PSA response, defined as a reduction ≥ 50% from baseline in the intention-to-treat population.
PSA Response
In the intention-to-treat population, PSA response was observed in 65 patients (66%) in the LuPSMA group vs 37 (37%) in the cabazitaxel group (difference = 29%, 95% confidence interval [CI] = 16%–42%, P = .0016). Among patients who received study treatment, PSA response was observed in 65 patients (66%) vs 37 patients (44%; difference = 23%, 95% CI = 9%–37%, P = .0016).
Radiographic or PSA progression-free survival was prolonged in the LuPSMA group (hazard ratio [HR] = 0.63, 95% CI = 0.46–0.86, P = .0028), with similar benefits observed in radiographic progression-free survival (HR = 0.64, 95% CI = 0.46–0.88, P = .0070) and PSA progression-free survival (HR = 0.60, 95% CI = 0.44–0.83, P = .0017).
KEY POINTS
- LuPSMA produced a higher PSA response rate vs cabazitaxel.
- Grade 3 to 4 adverse events were more common with cabazitaxel.
Adverse Events
Among patients receiving study treatment, grade 3 to 4 adverse events occurred in 33% of patients in the LuPSMA group vs 53% of the cabazitaxel group. The LuPSMA group had a higher rate of grade 3 to 4 thrombocytopenia (11% vs 0%) and lower rates of grade 3 to 4 neutropenia (4% vs 13%) and febrile neutropenia (0% vs 8%). Grade 3 to 4 diarrhea (5% vs 1%) and hematuria (6% vs 1%) were more common in the cabazitaxel group. No treatment-related deaths were observed.
The investigators concluded: “LuPSMA compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. LuPSMA is a new effective class of therapy and a potential alternative to cabazitaxel.”
Dr. Hofman, of Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the Prostate Cancer Foundation of Australia, Australian Nuclear Science and Technology Organization, Endocyte (a Novartis company), and others. For full disclosures of the study authors, visit thelancet.com.
