Biomarker Assessment for Benefit of LuPSMA vs Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer

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In a prespecified analysis from the Australian phase II TheraP trial reported in The Lancet Oncology, Buteau et al found that higher gallium-68–labeled PSMA-11 positron-emission tomography (PSMA-PET) mean standardized uptake values (SUVmean) were associated with a greater likelihood of prostate-specific antigen (PSA) response to lutetium-177–labeled PSMA-617 (LuPSMA) vs cabazitaxel in men with metastatic castration-resistant prostate cancer.

The previously reported results from the trial showed that LuPSMA improved PSA response rate (the primary endpoint) and progression-free survival compared with cabazitaxel.

Study Details

In the open-label multicenter trial, 200 patients were randomly assigned to receive LuPSMA at 6.0 to 8.5 GBq intravenously every 6 weeks for up to 6 cycles (n = 99) or cabazitaxel at 20 mg/m² every 3 weeks for up to 10 cycles. In the current study, an SUVmean ≥ 10 on PSMA-PET was evaluated as a marker for response to LuPSMA vs cabazitaxel. A metabolic tumor volume ≥ 200 mL on 2-[F-18]fluoro-2-deoxy-D-glucose PET (FDG-PET) was also assessed as a potential marker for PSA response.

Key Findings

Among 35 patients (35%) in the LuPSMA group and 30 (30%) in the cabazitaxel group with an SUVmean ≥ 10 on PSMA-PET, PSA response occurred in 32 (91%, 95% confidence interval [CI] = 76%–98%) vs 14 (47%, 95% CI = 29%–65%). Among 64 and 71 patients with an SUVmean < 10, response was observed in 33 (52%, 95% CI = 39%–64%) vs  23 (32%, 95% CI = 22%–45%). The odds ratios (ORs) for PSA response to LuPSMA vs cabazitaxel for patients with and SUVmean ≥ 10 vs those with an SUVmean < 10 were 12.19 (95% CI = 3.42–58.76) vs 2.22 (95% CI = 1.11–4.51; adjusted P = .039 for treatment-by-SUVmean interaction).

High-volume disease on FDG-PET (metabolic tumor volume ≥ 200 mL) was found in 30 patients (30%) in the LuPSMA group and 30 (30%) in the cabazitaxel group, with 69 and 71 having a metabolic tumor volume < 200 mL. For both treatment groups combined, PSA response was observed in 23 (38%, 95% CI = 26%–52%) of 60 patients with a metabolic tumor volume ≥ 200 mL and in 79 (56%, 95% CI = 48%–65%) of 140 with a metabolic tumor volume < 200 mL (OR = 0.44, 95% CI = 0.23–0.84, adjusted P = .035).

The investigators concluded: “In men with metastatic castration-resistant prostate cancer, PSMA-PET SUVmean was predictive of higher likelihood of favourable response to [LuPSMA] than cabazitaxel, which provides guidance for optimal [LuPSMA] use. High FDG-PET [metabolic tumor volume] was associated with lower responses regardless of randomly assigned treatment, warranting further research for treatment intensification. A strength of this analysis is the validation of pre-specified cutpoints within a multicentre, randomised, controlled trial. Quantitative PET parameters used, however, require specialised software and are not yet routinely available in most clinics.”

Michael S. Hofman, MBBS, of the Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for The Lancet Oncology article. For full disclosures of the study authors, visit

Disclosure: The study was funded by the Prostate Cancer Foundation of Australia, Endocyte (a Novartis Company), and others.

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