Several men have asked us if they are better off having 177Lu-PSMA-617 (Pluvicto) a radiopharmaceutical drug that treats PSMA positive metastases or Xofigo, a radiopharmaceutical drug that treats bone metastases. There is no simple answer, and the answer is not the same for each of us. Making a sound decision can be helped by understanding the mode of action and the limits of each treatment.
Pluvicto has two components, a drug that delivers, or targets, the therapy to the cancer cells and a radioactive particle that treats or destroys the cancer cells after they have been delivered to the mets.
In Pluvicto (177Lu-PSMA-617) the delivery vehicle (ligand) is PSMA-617 (aka, vipivotide tetraxetan), a drug that latches onto a protein called PSMA that is often found at high levels on the surface of prostate cancer cells. This protein, PSMA, is present in both bone and soft tissue prostate cancer mets, in around 80 to 90 percent of men.
The radioactive component or the actual treatment drug is lutetium-177.
For a more in-depth explanation see:
cen.acs.org/pharmaceuticals...
Xofigo mimics calcium, and calcium goes to bones. So, Xofigo specifically goes to the bones delivering the radiation treatment to the mets in the bones; Xofigo will not treat soft tissue mets. Xofigo does not require the presence of PSMA to successfully treat the bone metastases.
One treatment is not better than the other; they are different. Pluvicto and Xofigo have different targeting abilities. Pluvicto targets PSMA, but not all men express the protein PSMA. If you do express PSMA, verified by a positive PSMA scan, then Pluvicto can treat both bone and soft tissue mets. If you do not express PSMA, Pluvicto will not treat your mets. For men with only bone mets Xofigo will target and treat these mets.
After this discussion, we do need to add some additional complications.
• In conversation with some clinicians, I was told that in their practice they do not give Pluvicto immediately after Xofigo, but they will give Xofigo immediately after Pluvicto. I am unaware of a good reason for this, or any data supporting this sequencing, If I find any additional information or data I will share in an updated blog post.
• Xofigo combines well with some other medicines:
prostate cancer.news/2021/02...
• PSMA expression can be heterogeneous, so even one tumor part could express PSMA (and be treated), and part might not express PSMA and not be treated.
In summary, Xofigo only attacks bone metastases but attacks all of the bone mets you might have. Pluvicto only attacks cancer cells that express PSMA, and not all men and not all tumors express PSMA.
