Yervoy Can Benefit Certain mCRPC Patients with Few Mutations in Tumors, Trial Finds

Yervoy Can Benefit Certain mCRPC Patients with Few Mutations in Tumors, Trial Finds
Men with metastatic castration-resistant prostate cancer (mCRPC) showing evidence of active immune responses in their tumors live longer without disease progression after being treated with Yervoy (ipilimumab), a Phase 2 trial shows. These findings demonstrate that a subset of men with this form of advanced prostate cancer may benefit from treatment with immune checkpoint inhibitors — therapies that remove the “brakes” on the immune system to better fight cancer — despite having a low number of mutations in their tumors. Better responses were linked to higher numbers of immune T-cells in tumors. Trial findings were reported in the study, “Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab treatment of patients with prostate cancer,” published in the journal Science Translational Medicine. Certain types of malignancies, including melanoma or non–small cell lung cancer (NSCLC), tend to respond better to treatment with immune checkpoint inhibitors because they have a high number of genetic mutations, called a high tumor mutational burden. These mutations lead to the production of abnormal proteins, or neoantigens, that can easily be recognized and targeted by the immune system. “Because tumor neoantigens can be recognized by the immune system," the researchers wrote, "it is expected that the presence of preexisting immune [cell] infiltrates within the tumor microenvironment is also associated with clinical benefit to ICB [immune checkpoint inhibitors].” In the case of prostate cancer, however, these neoantigens are usually found in very low numbers, limiting patients’ response to these immunotherapies. Yet, two previous Phase 3 trials (NCT00861614 and NCT01057810) assessing the effects of Yervoy, an immun
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