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For Prostate Cancer Patients with Mismatch Repair Deficiency, Immunotherapy Alone?

All patients in the study will receive nivolumab, a form of immunotherapy, without the addition of ADT

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Bad things happen when the body’s DNA “quality control” mechanisms go awry. The job of these important genes, such as BRCA2, and proteins is to fix any errors that occur during DNA replications. When these “mismatch-repair” (MMR) functions are defective, “DNA mutations can accumulate,” says oncologist Mark Markowski, M.D., Ph.D., “and this can lead to cancer.”

As many as 5 percent of men with an inherited risk of prostate cancer have such a mutation. But this particular cloud may have a silver lining: “These tumors may be more susceptible to immunotherapy as a form of treatment,” Markowski says. Prostate cancer uses checkpoints – in effect, chemical handcuffs – to shackle powerful, cancer-fighting immune cells. Checkpoint inhibiting drugs unleash these immune cells and are FDA-approved as an option for men with mismatch repair-deficient (dMMR), metastatic castration-resistant prostate cancer (mCRPC).

However, says Markowski, “these patients are already on androgen deprivation therapy (ADT), which has many side effects and has a significant effect on quality of life.” Is there a better approach for this very specific group of patients?

In other words: “Is hormone suppression necessary for immunotherapy to work in these men?” With oncologist Emmanuel Antonarakis, M.D., Markowski is studying whether immunotherapy alone can be an effective treatment for dMMR cancer at an earlier stage – when prostate cancer is still hormonesensitive – “without the need for ADT.”

NIVO-BCR (NCT04019964) is a Phase 2 clinical trial for dMMR patients who have biochemical recurrence (a rising PSA) after treatment for localized cancer with prostatectomy or radiation. “All patients in the study will receive nivolumab, a form of immunotherapy, without the addition of ADT.” This trial has enrolled six of the planned 15 patients, and early results are exciting, says Markowski: “So far, our research team has observed deep and durable clinical responses – including two complete responses.” In additional research, the team is also looking for key biomarkers that can help predict response and identify patients who may benefit the most.

If you are interested in learning more about this study, please contact Rana Sullivan via email:


This beautiful picture was suggested by a patient, who prefers to remain anonymous. At left is Renee Drew, CRNP, Nurse Practitioner for the Prostate Group, and at right is Kristen Farling, DNP, MS., Certified Urologic Nurse Practitioner (CUNP). “They need to be recognized!” says our patient, because they had a great impact on his quality of life. “I was diagnosed, treated and cured of prostate cancer in 2021. Thank you, Brady! But the real story is the post-radiation therapy care provided by radiation oncology nurse Renee Drew and the Brady’s CUNP, Kristen Farling. Once a patient completes radiation therapy, there is a two-year period when side effects develop. In my case, I developed issues sustaining erections, and NP Farling immediately put me on injections. It changed my life! I am so grateful for these nurses’ dedication to my situation.” We at the Brady are proud of the care we offer, and extremely proud of our nurse practitioners, who offer unrivaled and compassionate care.

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