Until recently, medicine had little to offer men with advanced prostate cancer that no longer responds to hormone therapy, known as castration-resistant prostate cancer.
That’s rapidly changing, though, and men with castration-resistant prostate cancer have a growing number of treatment options to consider. That includes immunotherapy, which works by marshaling a man’s own natural defenses to fight the disease.
The first immunotherapy drug for prostate cancer, sipuleucel-T (Provenge), was approved by the U.S. Food and Drug Administration (FDA) in 2010 for treating men with castration-resistant prostate cancer who have few or no symptoms. Sipuleucel-T doesn’t cure prostate cancer, but appears to modestly prolong survival.
That success has helped to encourage other researchers to explore the potential of immune-boosting medicines. There are currently several other immunotherapy drugs in development for the treatment of castration-resistant prostate cancer, offering new hope for men faced with this diagnosis.
A brief history of immunotherapy
Immunotherapy is hardly a new idea. After all, vaccines, which were introduced in the late 18th century, are a form of immunotherapy. Vaccination is also known as immunization since it works by bolstering the body’s immune system, the network of structures and cells that protects the body from germs and other harmful intruders.
A vaccine contains dead or weakened germs; when injected into a healthy person, the immune system learns to recognize and destroy those germs, which helps prevent infections. Vaccines have dramatically reduced the incidence of once-common diseases such as measles, mumps, and rubella.
The immune system learns to spot germs, which carry proteins called antigens that the body identifies as foreign objects that need to be eliminated. Many cancer cells, including those in malignant prostate tumors, carry antigens, too.
The immune system can detect so-called cancer-associated antigens and respond by mounting an attack on tumors. However, the assault may not be potent enough to destroy a tumor, and cancer cells have evolved mechanisms that help them elude detection.
While vaccines are most commonly administered to prevent disease, the idea of using them to treat cancer dates back to at least 1891, when a doctor named William B. Coley at Memorial Hospital in New York City began injecting cancer patients with bacteria in the belief that the resulting attack by the immune system would eliminate the bacterial infection and shrink or eliminate the tumors at the same time.
Coley reported success in treating more than a thousand cancer patients over the years, but few doctors believed his claims, and the concept of immunotherapy was largely forgotten for decades.
A complex process
The idea of immunotherapy was resurrected in the late 20th century, which eventually led to the development of sipuleucel-T. Interestingly, men who receive this treatment provide the raw materials needed to, in essence, activate the therapy.
Here's how it works: A patient is first connected to a device that draws T cells and other cancer-fighting immune-system cells from his blood. These cells are sent to a laboratory, where they’re exposed to a protein called prostatic acid phosphatase (PAP), which occurs in most prostate cancers. This new formulation is infused back into the patient, with the goal of inducing the immune system to respond and attack the prostate tumor.
The benefit of sipuleucel-T was demonstrated in a 2010 clinical trial published in the New England Journal of Medicine. Researchers split 512 men with castration-resistant prostate cancer into two groups: About two-thirds of the volunteers were infused with sipuleucel-T treatments, while the remaining men received an inactive placebo treatment.
Although the drug didn’t appear to slow the spread of cancer, men treated with sipuleucel-T survived for about 26 months, while others given placebo treatment lived roughly 22 months. Men treated with the drug reported only mild to moderate side effects, such as chills, fever, and headache.
Adding a few extra months of life could be a precious gift for a man with castration-resistant prostate cancer. Moreover, this drug’s apparent benefit has helped to validate the concept of immunotherapy for treating prostate cancer, and the research continues.
Next up: PROSTVAC
Another form of immunotherapy in development that has shown promise in early clinical trials as a potential treatment for men with castration-resistant prostate cancer is known as PROSTVAC.
PROSTVAC is made with an inactivated virus, which has been genetically modified to carry prostate specific antigen (PSA), a protein produced by prostate cancer cells, as well as three other types of molecules designed to stimulate the immune system. In theory, the presence of PSA in PROSTVAC helps immune cells recognize prostate tumors and target them for attack.
In 2010, researchers from Boston’s Dana-Farber Cancer Institute and several other medical centers reported on the results of a preliminary trial of PROSTVAC in the Journal of Clinical Oncology. In the study, 82 men with castration-resistant prostate cancer were randomly chosen to receive PROSTVAC injections, while 40 other patients were given a placebo. Here again, the drug appeared not to affect tumor growth.
Yet three years later, 30 percent of the patients treated with PROSTVAC had survived, compared to 17 percent of men in the control group. Overall, the drug appeared to extend a man’s life by 8.5 months, on average.
A larger study of PROSTVAC is underway to confirm these findings, with results expected later in 2017.
Investigators are also studying whether immunotherapies currently used to treat other cancers may help vanquish prostate tumors. One candidate is ipilimumab (Yervoy), which is already approved for treating melanoma, a form of skin cancer.
Ipilimumab belongs to a new class of drugs called immune checkpoint inhibitors. Just as the immune system must turn on to attack an invader, it must also know how to turn off so that it doesn’t damage healthy tissue.
Molecules called immune checkpoints put the brakes on the body’s response when a potentially harmful invader has been eliminated. Some cancer cells are canny enough to take advantage of this braking mechanism by attaching themselves to receptors on T cells, causing them to turn off. Immune checkpoint inhibitors block cancer cells’ ability to shut down T cells, allowing the latter to go on attacking malignant tumors.
Ipilimumab targets a checkpoint called CTLA-4. A 2014 trial reported in Lancet Oncology included 799 men with castration-resistant prostate cancer whose cancer had spread to at least one bone after treatment with chemotherapy (docetaxel).
All the men had their bone metastases treated with radiation, but only half received ipilimumab treatment; the remaining men got inactive placebos. Men treated with ipilimumab did not live significantly longer than the others, but they experienced drops in PSA levels and growth of their tumors slowed. The drug also seemed to confer a greater benefit on men with less-advanced cancer. These promising clues have led to further research on ipilimumab for castration-resistant prostate cancer.
Several other approved melanoma drugs—pembrolizumab (Keytruda) and nivolumab (Opdivo)—target a different checkpoint, called PD-1. Studies show that both drugs can shrink solid malignant tumors, and each is currently in the early stages of testing in men with castration-resistant prostate cancer.
On the horizon
A number of other immunotherapy drugs for prostate cancer are in preliminary testing. What’s more, investigators are combining immunotherapies described here to see if they have complementary benefits.
For example, one early stage trial presented at a medical conference in 2015 suggested that pairing PROSTVAC and ipilimumab may extend survival in men with castration-resistant prostate cancer. Doctors are also studying whether immunotherapy might curb prostate cancer at an earlier stage, before it has spread to other organs.
If you have castration-resistant prostate cancer, be sure to discuss whether you’re a candidate for sipuleucel-T or experimental forms of immunotherapy with your doctor.
Learn more about how to choose the best prostate cancer oncologist and what you need to know when enrolling in a clinical trial..