KEY TAKEAWAYS
- A phase II, randomized, open-label trial evaluated whether PSMA and FDG-PET could be predictive and prognostic biomarkers while deciding on a viable treatment option for patients with mCRPC.
- The primary outcome measure of the trial was PSA RR with Pain Response, Objective Tumour Response Rate, PFS, and HRQoL, among the secondary measures.
- The study concluded that high FDG-PET MTV was associated with lower responses and more clinics require access to quantitative PET parameters
Phase II TheraP trial sought to examine the predictive and prognostic value of 2-[18F]fluoro-2-deoxy-D-glucose PET (FDG-PET) and gallium-68 [68Ga]Ga-PSMA-11 PET (PSMA-PET) imaging parameters in patients with metastatic castration-resistant prostate cancer eligible for cabazitaxel.
Patients were stratified patients by disease burden, prior enzalutamide or abiraterone treatment, and research site into 2 (1:1) arms. One arm receiving [177Lu]Lu-PSMA-617 (6.0-8.5 GBq intravenously for up to six cycles of 6 weeks), and the other receiving Cabazitaxel (20 mg/m2 intravenously for up to ten cycles of 3 weeks)
As a predictive biomarker for response to [177Lu]Lu-PSMA-617 instead of cabazitaxel, a SUVmean of 10 or greater on PSMA-PET was evaluated. An MTV (metabolic tumor volume) of 200 mL or more on FDG-PET was investigated on prespecified cutoff points as a prognostic indicator.
99 men were assigned to the [177Lu]Lu-PSMA-617 group, and 101 men were put to the Cabazitaxel group. The median follow-up was 18.4 months (IQR 12-8-21-8). High PSMA absorption (SUVmean of 10) was observed in 35 (35%) of 99 men assigned [177Lu]Lu-PSMA-617 and 30 (30%) of 101 men assigned cabazitaxel.
For men with SUVmean of 10 or greater, the odds of PSA response to [177Lu]Lu-PSMA-617 versus cabazitaxel were significantly higher (odds ratio [OR] 12.19 [95% CI 3.42-58.76] vs 2.22 [1.11-4.51]; padj=0.039 for treatment by-SUVmean interaction). The PSA response rate for [177Lu]Lu-PSMA-617 was 32 (91% [95% CI 76-98]) versus 14 (47% [29-65]). Among the patients with SUVmean less than 10, the PSA response rate was 33 (52% [39-64]) versus 23 (32% [22-45]).
PSA response rate was 23 (38% [95% CI 26-52] of 60 men versus 79 (56% [48-65]) of 140 men for both treatment groups combined for FDG-PET MTV of 200 mL or greater versus FDG-PET MTV of less than 200 mL (OR 044, 95% CI 0.23-0.84; padj=0.035). 30% of the participants in both arms had high-volume illness on FDG-PET (MTV 200mL).
The PSMA-PET SUVmean was a better predictor of a favorable response to [177Lu]Lu-PSMA-617 than cabazitaxel, thus, recommending [177Lu]Lu-PSMA-617 use. High FDG-PET MTV was associated with lower responses regardless of randomly assigned therapy, necessitating further research for treatment intensification. Access to quantitative PET parameters is crucial for clinics as they require specialized tools.
Source: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00605-2/fulltext
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03392428
Buteau, J. P., Martin, A. J., Emmett, L., Iravani, A., Sandhu, S., Joshua, A. M., Francis, R. J., Zhang, A. Y., Scott, A. M., Lee, S. T., Azad, A. A., McJannett, M. M., Stockler, M. R., Williams, S. G., Davis, I. D., Hofman, M. S., & TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (2022). PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial. The Lancet. Oncology, 23(11), 1389–1397. https://doi.org/10.1016/S1470-2045(22)00605-2
