New Gene Signature May Help Identify Prostate Cancer Patients Who Benefit From Immunotherapy

Researchers at University of Texas MD Anderson Cancer Center have identified a new gene expression signature that may help determine which patients with metastatic castration-resistant prostate cancer (mCRPC) are most likely to benefit from combination immunotherapy.

The findings, published in the journal Nature Communications, come from the Phase 2 CheckMate 650 clinical trial. Scientists evaluated the experimental combination of the immune checkpoint inhibitors Ipilimumab and Nivolumab in patients whose prostate cancer no longer responded to chemotherapy.

The study was led by Padmanee Sharma, a professor of Genitourinary Medical Oncology and Immunology at MD Anderson and director of scientific programs at the James P. Allison Institute.

Researchers found that some patients experienced significant and long-lasting responses to the immunotherapy combination, including tumor shrinkage, reduced prostate-specific antigen (PSA) levels, and extended overall survival. Response rates in the two immunotherapy groups reached 9.3% and 19.5%, with three patients achieving complete responses.

To understand why certain patients responded better than others, scientists analyzed tumor samples collected before treatment. Using advanced spatial profiling technology, they identified clusters of immune cells and a distinct gene expression signature associated with exceptional responses and longer survival.

The researchers believe this biomarker could eventually help doctors identify patients who are more likely to benefit from immunotherapy before treatment begins, while guiding others toward alternative therapies.

The trial enrolled 259 patients with advanced prostate cancer resistant to prior chemotherapy. Participants received either two different dosing schedules of combined immunotherapy, Ipilimumab alone, or standard chemotherapy. The study was not intended to directly compare treatment groups.

Serious treatment-related side effects occurred in 18.4% to 34.7% of patients. The most common complications included diarrhea, enterocolitis, and hypophysitis. Two treatment-related deaths were also reported during the trial.

Although overall response rates were relatively modest, researchers say the results suggest that a specific subgroup of patients with chemotherapy-resistant prostate cancer could benefit from combined immunotherapy. However, the treatment remains experimental and has not yet been approved by the U.S. Food and Drug Administration.

Future research will focus on validating the newly identified biomarker and confirming the effectiveness of this treatment approach in larger clinical studies.