A new treatment for advanced prostate cancer improves survival in phase 3 clinical trial

Radiation therapy is getting more precise, enabled by technologies that make it easier to kill tumors while sparing their surrounding tissues. Some newer therapies are even given intravenously instead of by machines, and they deliver radiation particles directly to the cancer cell itself. One of these new therapies — a sort of smart bomb targeted at malignant cells — is now generating promising data for men with the most aggressive prostate cancer.

In early June, investigators reported results from a phase 3 clinical trial showing that among men who received the experimental treatment, there was nearly a 40% reduction in deaths over the course of the study, compared to men who did not.

The treatment is called lutetium-177-PSMA-617, or LuPSMA, and it has two components: a compound that targets a cancer cell protein called prostate-specific membrane antigen, or PSMA, and a radioactive particle that destroys the cells. Healthy prostate cells don't contain PSMA, or do at very low levels. And some men with prostate cancer have more of the protein than others. Doctors can detect the protein using a specialized imaging scan.

To qualify for enrollment in the study, called the VISION trial, men had to be PSMA-positive. In all, 831 men were split into two groups: one group got the experimental treatment plus standard of care, while men in the control group got standard of care only. All the men had metastatic castration-resistant prostate cancer, meaning that the disease was spreading in the body and no longer responding to drugs that suppress testosterone (which fuels growing tumors).

Results after 21 months showed that cancer progression was delayed for longer among the LuPSMA-treated men: 8.7 months on average versus 3.4 months among the controls. The treatment was also associated with better overall survival: 15.3 months versus 11.3 months.

The VISION study comes on the heels of on an earlier phase 2 study (known as TheraP) that compared LuPSMA to chemotherapy in a population of 200 men. During that study, investigators monitored how the treatment affected prostate-specific antigen (PSA) levels, which usually increase if the cancer starts growing. In two-thirds of the LuPSMA-treated men, PSA levels fell by 50% or more. And as in the VISION trial, the experimental treatment was better at delaying cancer progression, which was confirmed with traditional imaging tests.

Dr. Thomas Hope, a radiologist and associate professor at the University of California, San Francisco, has been closely following this research. He says that TheraP is arguably the better study, since investigators in that case compared LuPSMA to chemotherapy, whereas standard of care in the VISION study excluded chemotherapy, immunotherapy, and other agents that doctors would otherwise try. In other words, Hope says, the VISION study compared LuPSMA to "nothing," which would ordinarily never happen. "So, the VISION trial doesn't really help you as much in terms of deciding which treatment to choose," he says.

LuPSMA was generally well-tolerated, but it also had side effects including fatigue, nausea, kidney problems, and bone marrow suppression. Dr. Hope says more research is needed to determine how and when to use the drug, "since if you have an eight-to-10-year expected lifespan, these side effects can be problematic."

If it's approved by the FDA, LuPSMA will be the first PSMA-targeted drug for prostate cancer to reach the market.