There are also ligands that attach to prostate cancer proteins other than PSMA, and radioactive elements other than Lu-177 that are in clinical trials. This is a rapidly developing field.
The new ligand is called PSMA-I&T (imaging and therapy) or sometimes PSMA-DOTAGA. The ligand used in most of the other studies was PSMA-617 (also known as PSMA-DKFZ) or PSMA-J591. The ideal ligand attaches strongly to PSMA in prostate cancer tumors and to nothing else. Importantly, it should not accumulate in the kidneys to a great extent because it could damage them.
Last year, the Central Clinic of Bad Berka, Germany reported on 56 patients treated with Lu-177-PSMA-I&T (see this link). 80% of treated patients had a PSA response and toxicity was minor. Heck et al. at the Technical University of Munich reported on 19 metastatic castration-resistant patients who were treated with 7.4 GBq per cycle and up to 4 cycles.
- In 56%, PSA decreased by at least 30%
- In 33%, PSA decreased by at least 50%
- In 11%, PSA decreased by at least 90%
- Complete remission of metastases in 5%
- Metastases stayed stable in 63%
- Metastases progressed in 32%
- Performance status was stable or improved in 74%
- In those with bone pain, it was reduced partially or completely in 58%
- Mild (Grade 1 or 2) toxicities included dry mouth (37%), anemia (32%), and platelet loss (25%)
- There were no severe (Grade 3 or 4) toxicities.
- There was no kidney toxicity up to 40 GBq (see this link)
- In 38%, PSA decreased by at least 50%
- Median clinical progression-free survival was 4.1 months
- Median overall survival was 12.9 months
- Treatment-emergent hematologic grade 3/4 toxicities were anemia (9%), thrombocytopenia (4%), and neutropenia (6%)
- 68% of patients had some PSA decline
- 37% of patients had a PSA decline of at least 50%
- More patients had a PSA decline with the PSMA-I&T and PSMA-617 ligands, but there was a wide range of outcomes
These early indicators look good. Even if it just stabilizes performance status and mitigates bone pain in these end-stage patients, there is an important benefit. Of course, what we really want to see is evidence that it increases overall survival
While PSMA-I&T was developed to be a good ligand for imaging purposes as well as therapeutic purposes, a recent study found that, when used with Ga-68 (a positron emitter), PSMA-HBED-CC (also known as PSMA-11) was slightly better at detecting metastases (see this link). Another PSMA ligand, DCFPyL, that incorporates the positron emitter F18 into the ligand more tightly (avoiding chelation, which can easily be reversed), seems to be superior to the Ga-68-PSMA-HBED-CC PET tracer (see this link). Both DCFPyL PET and Ga-68-HBED-CC PET are in numerous clinical trials in the US and Canada. Lu-177 is a gamma emitter that can be seen by a gamma camera or via SPECT. However, it is usually used in conjunction with a positron-emitter in order to obtain a superior image.
Readers may wish to read these other articles on this subject:
Will Lutetium-177-anti-PSMA be the next Xofigo?
Lu-177-PSMA: another update
First in-human trial of Actinium-225-PSMA-617
Ac-225-PSMA-617 extends survival (update)
I-131-MIP-135, a new radiopharmaceutical, in clinical trial at Memorial Sloan Kettering