According to a recent publication about the phase 2 TheraP trial, the PSA response rate was higher with the investigational radioligand therapy 177Lu-PSMA-617 and had less adverse severe side effects than cabazitaxel (Jevtana) in men with metastatic castration-resistant prostate cancer (mCRPC). These findings were published in the Lancet1 and presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.2
The findings showed a PSA response rate of 66% with LuPSMA compared with 37% with cabazitaxel. The trial also showed that among the men who received LuPSMA compared to Jevtana, the LuPSMA group experienced less serious side effects (grade 3/4 AEs, which are the most serious). Serious side effects occurred in 33% of men having LuPSMA versus 53% of the men taking Jevtana.
“This phase 2 study provides evidence that 177Lu]Lu-PSMA-617 is a potential alternative to cabazitaxel in men with metastatic castration-resistant prostate cancer, with greater activity but less severe side-effects and improvements in patient-reported outcomes,” first author Michael S. Hofman, FRACP, MBBS, Peter MacCallum Cancer Center, Melbourne, Australia, and coauthors wrote.”
The TheraP trial enrolled 200 men with mCRPC who progressed after having chemotherapy with docetaxel and who had prostate cancer that generated high levels of PSMA3. Since not all prostate cancer causes PSMA, the expression of PSMA was confirmed by prior imaging with 68Ga-PSMA-11 and 18F-FDG PET/CT.
Over 90% of the men in both arms of the trial had already taken other second-line treatments, including abiraterone acetate (Zytiga), enzalutamide (Xtandi), or both.
The men were randomized in a 1:1 ratio to LuPSMA (n = 99) or Jevtana (n = 101). Study treatment occurred at 11 clinical locations in Australia. In the LuPSMA cohort, men received posttreatment SPECT/CT scans after each cycle. Men who had an exceptional response having their treatment paused. Treatment would subsequently resume at the time of PSA progression.
PSA response rate showing a reduction of 50% or more was the primary study endpoint. Critical secondary efficacy endpoints included progression-free survival, grades of side effects (AEs), and overall survival (OS).
The trial showed that the LuPSMA treatment delayed prostate cancer progression versus Jevtana, with a comparable benefit observed in radiographic progression-free survival and PSA progression-free survival. In other words, men who received LuPSMA had less cancer progression, as shown on their scans, and did better in having their PSAs controlled.
In addition to these benefits, men who had LuPSMA had less serious side effects than those who had Jevtana.
LuPSMA treatment is not yet approved in the United States. Most likely, it will be approved, but not for a while. Cancer ABCs is aware that there are men who have had LuPSMA treatment by going to other countries like Australia and Germany.
PSMA scans are ahead of PSMA treatment approvals in the United States. In December 2020, the FDA approved gallium 68 PSMA-11 as the first drug for positron emission tomography (PET) imaging of PSMA-positive lesions in men with prostate cancer.
The FDA is currently reviewing a new drug application for the PSMA-targeted PET imaging agent 18F-DCFPyL (PyL) for prostate cancer under the Prescription Drug User Fee Act. The FDA is scheduled to decide on the application by May 28, 2021.
Reference
1. Hofman MS, Emmett, L Sandhu S, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomized, open-label, phase 2 trial. Lancet. 2021;397(10276):797-804. doi: 10.1016/S0140-6736(21)00237-3
2. Hofman MS, Emmett L, Sandhu SK, et al. TheraP: A randomized phase II trial of 177Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel: initial results (ANZUP protocol 1603). Presented at 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 5500.
3. PSMA is a protein that is often, but not always, expressed on the cell surface of prostate cancer cells. The principle behind LuPSMA therapy is that the PSMA expressed is used as a target allowing a therapeutic to be delivered specifically to the prostate cancer cell expressing the protein.
