Identifying Patients for Immunotherapy
Patients with metastatic castration-resistant prostate cancer (mCRPC) usually have limited response to immunotherapy. However, a Phase II trial found that an immunotherapy drug benefitted certain patients with this type of prostate cancer. The patients had a specific type of immune activation prior to treatment. If validated with a larger clinical trial, this could be an exciting discovery.
The drug studied in the trial was ipilimumab (brand name Yervoy). The drug is used in patients with metastatic melanoma. It is thought to enhance the body’s immune response by activating T cells, which help fight cancer cells.
Cancers such as melanoma and lung cancer tend to have the strongest response to immune checkpoint inhibitors such as ipilimumab, because these cancers have high levels of gene mutations. The immune system can recognize these mutations as abnormal, and immunotherapy can enhance this.
Prostate cancers tend to have lower mutation levels. However, some patients with mCRPC in other trials have had good responses to immunotherapy. This study hoped to identify which prostate cancer patients with low levels of gene mutations could still benefit from immunotherapy.
The authors of the study analyzed data on 29 patients with mCRPC who received ipilimumab. Nine patients were in a “favorable” group with six months or longer before their disease progressed and overall survival of at least a year.
When compared to patients who had the worst results in the trial, the study found that patients in the “favorable” group had differences in their immune system before starting the treatment, which could be measured by biomarkers. For example, favorable group patients had a higher density of cytotoxic and memory T cells, and their T cells were able to recognize and respond to tumor cells in a way that other patients’ T cells did not.
The authors are planning to explore these biomarkers further in a larger Phase III trial. If validated, this could offer a new personalized medicine approach for men with mCRPC who have these biomarkers.
The research was led by scientists at The University of Texas MD Anderson Cancer Center and published in Science Translational Medicine in April.
Metastatic castration-resistant prostate cancer is a form of advanced disease in which the cancer has spread beyond the prostate and no longer responds to hormonal therapy, also known as hormone therapy or androgen-deprivation therapy (ADT).