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2019 GU Cancers Symposium: CheckMate 650: Nivolumab and Ipilimumab in Metastatic, Castration-Resistant Prostate Cancer

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Key Points

  • Among castration-resistant patients who had progressed after second-generation hormonal therapy (cohort 1), 25% (8 of 32) saw a response from the immunotherapy combination at a median follow-up of 11.9 months.
  • Among those who progressed after chemotherapy and hormonal therapy (cohort 2), 10% (3 of 30) had a response at median follow-up of 13.5 months.
  • 42% of patients in cohort 1 and 53% in cohort 2 experienced grade 3–5 adverse events.

Some patients with metastatic prostate cancer respond to a combination of immune checkpoint inhibitors after treatment with hormonal therapy and chemotherapy has not been successful in treating their disease, according to early results from the phase II CheckMate 650 trial presented by Sharma et al the 2019 Genitourinary Cancers Symposium (Abstract 142).

Principal investigator Padmanee Sharma, MD, PhD, Professor of Genitourinary Medical Oncology and Immunology at The University of Texas MD Anderson Cancer Center, said the results of combining the CTLA-4 blocking drug ipilimumab with the programmed cell death protein 1 (PD-1) inhibitor nivolumab provide an encouraging step for a cancer that has been highly resistant to immune checkpoint therapies.

CheckMate 650 was organized after research published by Gao et al in Nature Medicine provided scientific underpinning for the combination in prostate cancer.

CheckMate 650 Findings

Among castration-resistant patients who had progressed after second-generation hormonal therapy (cohort 1), 25% (8 of 32) saw a response from the immunotherapy combination at a median follow-up of 11.9 months. Among those who progressed after chemotherapy and hormonal therapy (cohort 2), 10% (3 of 30) had a response at median follow-up of 13.5 months.

“This was the first combination trial of two immune checkpoint therapies in prostate cancer,” Dr. Sharma said in a statement. “These results support the idea that immune checkpoint blockade can play an important role in the treatment of these patients and provide the foundation to test this strategy in a larger clinical trial.”

There were four patients who experienced a complete response—two in each cohort—among the 62 patients who could be evaluated for tumor growth.

Side effects from the combination were consistent with those experienced in previous combination trials for other cancers, with 42% of patients in cohort 1 and 53% in cohort 2 experiencing grade 3–5 adverse events. Among cohort 1, 33% had to discontinue participation due to adverse events, with 35.6% having to withdraw from cohort 2. The most common adverse events were diarrhea, fatigue, skin rash, nausea, and hypothyroidism. Four patients died from treatment-related adverse events—two in each cohort.

Disease progression was the most common reason to leave the trial, with 51.1% of cohort 1 and 44.4% of cohort 2 discontinuing for that reason.

The researchers also analyzed a number of biomarkers and found that higher tumor mutational burden was associated with response.

Dr. Sharma said investigators and are designing a follow-up trial that includes altering either the dosing or scheduling of ipilimumab with the goal of reducing side effects. Patients in the current trial, CheckMate-650, will be assessed for overall response rate and radiographic progression-free survival as primary endpoints and overall survival as a secondary endpoint. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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