What is Pluvicto?
A) A newly discovered planet
B) A Disney cartoon character
C) A treatment that targets prostate cancer cells anywhere in the body.
If you guessed C, you are correct!
Metastatic prostate cancer (mPCa) is considered incurable. There are new chemotherapies, PCa vaccines and immunotherapies that can add months to a patient’s life. The disappointing news is that mPCa eventually overcomes these treatments—and for many patients, the side effects can be harsh.
Now there’s Pluvicto, an intravenous treatment that delivers a radioactive punch to individual mPCa cells. On March 23, 2022, the U.S. Food and Drug Administration (FDA) announced that it had approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.[i]
In other words, Pluvicto is for patients who meet certain conditions. Let’s look at it, piece by piece:
- PSMA-positive means that a special type of imaging called a PSMA PET/CT scan has detected remote locations of PCa tumors that have spread from the original prostate tumor. PSMA stands for Prostate Membrane Specific Antigen. The membrane, or outer cell surface that encloses the cell’s content, has “ID tags” in the form of a protein specific to that cell. This is true of all prostate cells, but when they mutate into PCa cells, PSMA becomes highly abundant—a sort of red flag that such cells are enemies.
- PSMA PET/CT scans involve an IV injection of a detection “cocktail” that is made up of a substance that the PSMA on cancer cells readily bind to, such as a type of sugar molecule the cell recognizes as a fuel it can use to survive and multiply, and a radioactive isotope such as Gallium 68 that lights up on a PET/CT scan. The sheer quantity of PSMA amassed on a cancer cell gathers far more isotope than the PSMA on a normal cell, causing the cancer cells to dramatically light up on the scan. Think of it like a WWII radium dial on an Air Force wrist watch that would glow in the dark so pilots flying darkened bombers on night raids could track the time.
So far, then, the FDA statement is saying that Pluvicto is for patients whose metastatic disease has been proven by a PSMA PET/CT scan. Now, here’s the next condition:
- Metastatic castration-resistant PCa (mCRPC) means that the patient has been on androgen deprivation therapy (ADT), whether constant or intermittent, for a long period of time until it stopped working. Remember that ADT or hormone therapy deprives PCa cells of the testosterone they use to energize their growth and duplication. Thus, ADT is also called chemical castration, and it uses a pharmaceutical to create the same impact as surgically removing a man’s testicles to stop testosterone production. Either way, the biochemical pathway by which PCa cells obtain and use testosterone is inhibited, so the treatment initially stops the tumor in its tracks. However, eventually the cancer outsmarts the ADT and resumes its destructive progress, thus becoming castration-resistant. This condition must be met.
- Next, as the Prostate Cancer Foundation explains, “Currently, taxane chemotherapy, given with prednisone, is the standard of care for men with metastatic prostate cancer that has spread and is progressing despite hormone therapy. Taxane chemotherapy agents approved for the treatment of advanced prostate cancer include docetaxel (Taxotere®) and cabazitaxel (Jevtana®).” While these agents have shown “unprecedented survival advantages” in clinical trials, making them an obvious treatment choice, “not all men respond and resistance invariably emerges.”[ii]
In short, the FDA has approved Pluvicto for mCRPC patients for whom the two standard of care approaches to prolonging lives are no longer effective. It works in a way similar to PSMA PET/CT scans. The drug is a cocktail of a PSMA-attractive molecule and a different type of radioisotope that delivers a small but lethal radiation dose to individual mPCa cells.
Clinical trial results for Pluvicto
The clinical trial upon which the FDA based its approval involved 551 men who received Pluvicto plus the current best standard of care vs. 280 men who received only the current best standard of care. All patients enrolled in the trial met the strict inclusion criteria regarding previous treatments that had failed. The results showed that the men who received Pluvicto had an average overall survival time of 15.3 months compared to 11.3 months for those who did not receive Pluvicto.
Those receiving Pluvicto had, on average, a higher rate of side effects which included fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. Roughly 30% of Pluvicto patients also had abnormal blood test results. The FDA cautions that the radioactive isotope used in Pluvicto, different from the imaging isotopes, may result in risk from radiation exposure.
Pluvicto offers a promising new direction that is well worth continued research. It’s a smart bomb approach to conquering mPCa cells that have circumvented the effects of ADT and taxane-based chemotherapies.
We will continue to track clinical successes in the search to cure the incurable. Please continue to visit our blog for updates.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
[ii] Gjyrezi A, Xie F, Voznesensky O, Khanna P et al. Taxane resistance in prostate cancer is mediated by decreased drug-target engagement. J Clin Invest. 2020 Jun 1;130(6):3287-3298.