Advanced Prostate Cancer: Experts say this double therapy can help

A common treatment for men with advanced or metastatic prostate cancer is hormone therapy.

ISLAMABAD, (Online) - Prostate cancer is the second most common cancer in men in the United States, after skin cancer, and it causes around 34,700 deaths per year, according to the American Cancer Society.

A common treatment for men with advanced or metastatic prostate cancer is hormone therapy, also known as androgen deprivation therapy or androgen suppression therapy.

Androgens — hormones such as testosterone and dihydrotestosterone (DHT) — stimulate certain prostate cancer cells to grow. The testicles make most of the androgens in the body, but the adrenal glands and prostate cancer cells themselves also produce these hormones.

Androgen deprivation therapy uses surgery or medicines to block the production or action of androgens. This deprives prostate cancer cells of these hormones, which can cause the cancer to shrink or grow more slowly.

Prostate cancers that need androgens to grow are known as hormone-sensitive prostate cancers.

For many years, androgen deprivation therapy was used alone to treat metastatic prostate cancer, an advanced cancer that has spread from the prostate to other parts of the body.

More recently, clinical trials have shown that using another type of hormone therapy alongside androgen deprivation therapy can improve the survival of men with this type of prostate cancer.

The results of one of these trials, published March 27 in The Lancet Oncology, support the use of the drug enzalutamide alongside androgen deprivation therapy for men with metastatic prostate cancer.

This trial, known as ENZAMET, was carried out by researchers around the world and led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group.

Combination therapy improves survival rates

Enzalutamide (brand name Xtandi) is an antiandrogen, a drug that prevents androgens from binding to receptors in certain prostate cancer cells.

It is approved by the Food and Drug Administration to treat metastatic hormone-sensitive prostate cancer. It is also approved to treat castration-resistant prostate cancer, a type of cancer that continues to grow even when the androgen levels are very low.

The ENZAMET trial included over 1,000 men with prostate cancer, who were randomly assigned to receive either a standard non-steroidal antiandrogen or enzalutamide.

Researchers found that men in the trial who received androgen deprivation therapy plus oral enzalutamide had a 67% survival rate after five years.

In contrast, men who received androgen deprivation therapy plus a weaker commonly used antiandrogen had a five-year survival rate of 57%.

“These high-level findings indicate that the addition of enzalutamide should be considered as a treatment option for any patient able to receive it,” Dr. Christopher Sweeney, director of the South Australian immunoGENomics Cancer Institute (SAiGENCI) that operates within the University of Adelaide, said in a news release.

Some patients in the trial also underwent chemotherapy with docetaxel (brand name Taxotere), which is used to treat metastatic prostate cancer that has not responded to lower testosterone levels (castration-resistant cancer).

Adding enzalutamide to a patient’s treatment was beneficial, “regardless of when the cancer was found to have spread, or how much was present, or whether people also received docetaxel chemotherapy,” Sweeney said in the release.

“The exploratory findings [of this trial] indicate it might not be necessary to add other treatments like chemotherapy,” he added. Second-generation antiandrogens offer benefit

In 2019, preliminary findings from the ENZAMET trial were published in The New England Journal of Medicine.

This earlier analysis also showed a benefit of giving enzalutamide to men with metastatic hormone-sensitive prostate cancer who were receiving androgen deprivation therapy.

Dr. Przemyslaw Twardowski, a medical oncologist and professor of medical oncology at Saint John’s Cancer Institute at Providence Saint John’s Health Center in Santa Monica, Calif., who was not involved in the new study, told Healthline that the Lancet Oncology paper more or less confirms what was already known about the benefits of enzalutamide for men with metastatic prostate cancer.

“It’s one of many studies that indicate that early treatment intensification for patients with metastatic prostate cancer is beneficial,” he said. In particular, “adding enzalutamide early on in the treatment of metastatic prostate cancer improves survival,” he said, “versus waiting until the cancer becomes resistant to standard hormone therapy and then adding enzalutamide.”

Other clinical trials have shown a similar benefit of enzalutamide. For example, the U.S.-based ARCHES trial found that enzalutamide plus androgen deprivation therapy reduces the risk of prostate cancer progressing and men dying from their cancer, compared to treatment with only standard hormone therapy.

These results were published in 2019 in the Journal of Clinical Oncology.

Twardowski said many of the second-generation androgen receptor antagonists — which include apalutamide and darolutamide — provide similar benefits as enzalutamide, with minor differences in the side effects associated with them.

One thing that researchers achieved with the recent ENZAMET analysis is looking at the benefits of enzalutamide for specific patient subgroups, such as whether or not they received chemotherapy, or how far their cancer had spread.

The new analysis shows that “the benefits [of adding enzlutamide] seem to be very consistent across the various subgroups,” said Twardowski.

The new analysis supports double therapy for metastatic hormone-sensitive prostate cancer, specifically enzalutamide and standard androgen deprivation therapy.

But Twardowski said more research is needed to know if there is additional benefit to triple therapy — such as adding chemotherapy on top of these other two treatments — in particular, for patients with cancer that has spread more widely.

“In other words, should we be combining standard hormone therapy, plus chemotherapy, plus second-generation hormone therapy?” he said. “Right now, it is hard to figure out from these studies how far we should be intensifying treatment.”