#pluvicto

The Nuclear Medicine Therapy Centre at FMRI is one of the pioneers in medical tourism for patients with prostate cancer and neuroendocrine tumors. The center provides you with an effortless way to understand and go through your treatment process including pick-up/drop, and visa on arrival.  We ensure that the treatment is effortless and budget-friendly and are there with you to help navigate everything. 

Several men have asked us if they are better off having 177Lu-PSMA-617 (Pluvicto) 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. 

Like some other radiopharmaceuticals, both of these treatments have 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 the case of 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. The protein, PSMA, is present in bone and soft tissue prostate cancer Mets, but only 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...

The delivery vehicle for Xofigo mimics calcium, and calcium goes (targets) bones. So, Xofigo specifically goes to the bones, and the attached radiation treatment treats the Mets in the bones; Xofigo will not treat soft tissue Mets.   

 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 the Mets.

After this discussion, we do need to add some additional complications.

• You cannot get Pluvicto soon after Xofigo, but you can get Xofigo after Pluvicto. I am unaware of a good reason for this - it was just how Pluvicto was tested and approved.

• 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.   

Novartis and Advanced Accelerator Applications, the radioligand business of Novartis, has announced that their investigational treatment, Pluvicto™, was approved by the FDA.   Pluvicto, lutetium Lu 177 vipivotide tetraxetan (formerly referred to as 177Lu-PSMA-617) is the first approved targeted radioligand therapy for the treatment of men with progressive, PSMA‑positive metastatic castration-resistant prostate cancer. 

Specifically, the approval is only for the treatment of men with advanced prostate cancer that is metastatic (spread outside the prostate gland), castrate resistant (no longer responding to primary hormone therapy), and be prostate-specific membrane antigen (PSMA) positive.   The approval also includes the requirement that the men should have already been treated with other anticancer treatments (androgen receptor pathway inhibition and taxane-based chemotherapy). 

To confirm that the prostate cancer is PSMA positive, meaning that the tumor expresses the target, PSMA, along with the approval of Pluvicto, the FDA also approved a complementary diagnostic imaging agent, Locametz.   Locametz is a radiolabeling method using gallium-68 to confirm and identify PSMA-positive lesions. Not all prostate cancer expresses PSMA. Since Pluvicto uses PSMA as a target, it will only be effective for those PSMA positive cancers.

The approval was based on pivotal Phase III VISION trial, where men with pre-treated PSMA-positive mCRPC who received Pluvicto plus standard of care had a statistically significant reduction in risk of death over those just treated with the standard of care (SOC).

The most common adverse events (all grades) in the Pluvicto arm of the study were fatigue (43%), dry mouth (39%), nausea (35%), anemia (low red blood cell counts) (32%), decreased appetite (21%), and constipation (20%).