Findings from the phase 2 TheraP trial showed 177Lu-PSMA-617 to result in a higher prostate-specific antigen response rate vs with cabazitaxel in patients with metastatic castration-resistant prostate cancer.
PSMA-PET standardized uptake value (SUVmean) was a predictive biomarker for response to 177Lu-PSMA-617 compared with cabazitaxel (Jevtana) for men with metastatic castration-resistant prostate cancer (mCRPC), according to findings from the phase 2 TheraP trial (NCT03392428).1
Regardless of randomly assigned treatment, high FDG-PET metabolic tumor volume (MTV) was associated with lower responses. These findings warrant further research examining treatment intensification in mCRPC.
“Although 177Lu-PSMA-617 resulted in a higher [prostate-specific antigen] response rate compared with cabazitaxel in the TheraP trial, the use of an additional predictive biomarker could identify the subgroup of men who might benefit most of all in terms of response rate. For these men, providing 177Lu-PSMA-617 could be prioritized,” wrote study authors led by James P. Buteau, MD, Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre.
The multicenter, open-label, randomized, phase 2 TheraP trial examined men with metastatic castration-resistant prostate cancer following treatment with docetaxel who were suitable for cabazitaxel. Across 11 hospitals in Australia, patients aged 18 years old or older with adequate hematological, renal, and liver function, and an ECOG performance status of 0-2 were enrolled.
A total of 200 patients were randomly assigned in a 1:1 ratio and given either cabazitaxel (n = 101) at an intravenous (IV) dose of 20 mg/m2 every 3 weeks for up to 10 cycles or 177Lu-PSMA-617 (n = 99) at 8.5 GBq every 6 weeks for up to 6 cycles. Then, the dose was decreased by 0.5 GBq every cycle down to a minimum of 6.0 GBq.
Randomization was stratified by disease burden, previous treatment with enzalutamide (Xtandi) or abiraterone (Zytiga), and study site using minimization with a random component.
The primary study end point of the study was prostate-specific antigen (PSA) response rate defined as the number of patients with a PSA reduction of at least 50% from baseline and secondary end points included radiographic progression-free survival (rPFS) and PSA PFS.
At baseline, characteristics of patients in each group were similar, including the mean PSMA-PET MTV for patients in the cabazitaxel to be 949 mL and 1082 mL in the 177Lu-PSMA-617 cohort, respectively. The mean PSMA-PET SUVmax was 57 for patients in the cabazitaxel cohort and 66 for the 177Lu-PSMA-617, the PSMA-PET SUVmean was 9.3 and 9.7, the mean FDG-PET MTV was 219 mL and 187 mL, and the mean FDG-PET SUVmax was 11 in each cohort. Further, the FDG-PET SUVmean was 4.36 and 4.42 across each respective arm. In the cabazitaxel arm, the percentage of patients who had a FDG MTV of 200 mL or more was 30% as well as 30% in the 177Lu-PSMA-617 arm.
When combining both arms, the PSA response rate was 38% (95% CI, 26%-52%) for patients with an FDG-PET MTV of 200 mL or more vs 56% (95% CI, 48%-65%) for those with an FDG-PET MTV of less than 200 mL (odds ratio, 0.44; 95% CI, 0.23-0.84; P = .035).
For patients treated with 177Lu-PSMA-617 vs cabazitaxel, rPFS rates showed the HR to be 0.46 (95% CI, 0.25-0.84) for patients with a PSMA-PET SUVmean of 10 or more and 0.85 for those with a PSMA-PET SUVmean of less than 10 (95% CI, 0.59-1.24).
Overall, results were similar in the PSA PFS analysis of patients with a PSMA-PET SUVmean of at least 10 (HR, 0.45; 95% CI, 0.25-0.80) and patients with a PSMA-PET SUVmean of less than 10 (HR, 0.77; 95% CI, 0.53-1.12). Moreover, patients who had a FDG-PET MTV 200 mL or more often had a worse rPFS (HR, 1.79; 95% CI, 1.28-2.52; P = .0008) as well as a worse PSA PFS outcome (HR, 1.44; 95% CI, 1.03-2.02; P = 0.031).
“Furthermore, FDG-PET could identify men with metastatic castration-resistant prostate cancer who might have a worse prognosis, regardless of treatment. Trials exploring treatment intensification in men with high FDG-PET MTV, such as higher doses of 177Lu-PSMA-617, shorter intervals of 177Lu-PSMA-617 administration, or combination therapies, are warranted,” concluded the study authors.