Prostate cancer is one of the most common cancers affecting men worldwide. While many cases grow slowly and can be treated successfully, some forms of the disease are much more aggressive.
When prostate cancer spreads beyond the prostate gland to other parts of the body, it becomes much harder to treat. Doctors have made major advances in recent years, but preventing the disease from becoming resistant to treatment remains one of the biggest challenges.
A new international clinical trial led by researchers at the University of Utah’s Huntsman Cancer Institute has produced encouraging results for men with a particular type of advanced prostate cancer.
The study found that combining two existing cancer drugs significantly reduced the risk of disease progression or death in patients whose tumors carried certain genetic mutations.
The findings were published in the New England Journal of Medicine and were also presented at the American Society of Clinical Oncology Annual Meeting.
The Phase III clinical trial, known as TALAPRO-3, involved 599 men from 266 medical centers around the world. The study focused on patients with metastatic castration-sensitive prostate cancer.
This type of prostate cancer has already spread beyond the prostate but still responds to treatments that reduce male hormones, especially testosterone.
Prostate cancer cells often depend on male hormones, known as androgens, to grow and survive. Standard treatment usually involves lowering testosterone levels or blocking the cancer’s ability to use these hormones.
This approach can slow cancer growth for years. However, many tumors eventually adapt and continue growing despite hormone treatment. When that happens, the disease becomes castration-resistant prostate cancer, which is generally more difficult to control.
Researchers have been searching for ways to delay this transition and keep patients responding to treatment for as long as possible.
The TALAPRO-3 study examined two medications. The first was enzalutamide, sold under the brand name XTANDI. This drug blocks the androgen receptor, preventing testosterone and related hormones from stimulating cancer cells.
The second drug was talazoparib, marketed as TALZENNA. Talazoparib belongs to a group of medicines known as PARP inhibitors, which prevent cancer cells from repairing damaged DNA.
The trial specifically enrolled patients whose cancers carried inherited or acquired mutations in genes involved in DNA repair. These included BRCA1, BRCA2, and several related genes.
These mutations are present in roughly one-quarter to one-third of patients with metastatic castration-sensitive prostate cancer and are often associated with more aggressive disease and poorer outcomes.
Participants were randomly assigned to receive either enzalutamide alone or the combination of enzalutamide and talazoparib.
The results were striking. The combination treatment reduced the risk of disease progression or death by 52% compared with standard treatment alone. Researchers measured progression using imaging tests such as CT scans and bone scans, which can reveal whether cancer has spread or grown.
After three years of follow-up, 77% of patients receiving the combination treatment remained free of radiographic disease progression. In contrast, only 56% of patients receiving enzalutamide alone achieved the same outcome.
Importantly, the benefits were seen across patients with BRCA mutations as well as those with other related genetic changes. This suggests that a broad group of patients with DNA repair gene mutations may benefit from the combination therapy.
Another encouraging finding involved quality of life. Patients receiving the two-drug combination generally maintained similar levels of daily functioning and well-being compared with those receiving standard therapy alone. This means the improved cancer control did not appear to come at the cost of significantly worsening most patient-reported outcomes.
The findings highlight the growing importance of genetic testing in prostate cancer care. By identifying patients with specific gene mutations, doctors can tailor treatments to match the biology of an individual’s cancer. This approach, often called precision medicine, aims to deliver more effective therapies to the patients most likely to benefit.
The TALAPRO-3 study builds on earlier research known as TALAPRO-2, which investigated the same drug combination in patients whose disease had already become castration resistant. Results from that earlier trial helped support FDA approval of the treatment combination in 2023 for certain patients with advanced prostate cancer.
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Source: University of Utah Huntsman Cancer Institute.
