Prostate Cancer Coverage from Every Angle

Combination Therapy for Enzalutamide-Resistant Prostate Cancer

By: Cordi Craig
Posted: Friday, March 13, 2020

The results of KEYNOTE-199, a multicohort phase II study, suggested that following enzalutamide resistance, the combination of pembrolizumab and enzalutamide showed moderate antitumor activity among patients with metastatic castration-resistant prostate cancer. Julie Nicole Graff, MD, of the Oregon Health and Science University, Portland, and colleagues found that the combination therapy appeared to have a manageable safety profile. The findings were presented at the 2020 Genitourinary (GU) Cancers Symposium in San Francisco (Abstract 15) and published in the Journal of Clinical Oncology. Based on these results, a phase III trial is underway.

The researchers evaluated 126 patients with Response Evaluation Criteria in Solid Tumors–measurable disease (n = 81) and bone-predominant disease (n = 45) from cohorts 4 and 5, respectively. Eligible patients had achieved clinically meaningful responses to enzalutamide with or without prior abiraterone. All of the patients experienced disease progression after enzalutamide treatment.

After a median follow-up of 13.7 months, 107 patients discontinued treatment, primarily due to disease progression. The overall response rate was 12% in cohort 4, including two complete responses and eight partial responses. The disease control rate was 51% for both cohorts. More than half of the patients in cohort 4 (53%) achieved reduction in target lesions. The progression-free survival rate at 12 months was 17% in cohort 4 and 23% in cohort 5.

Adverse events of any grade were reported in 75% of those in cohort 4 and 69% of those in cohort 5. Severe adverse events occurred in 26% and 24% of patients in cohorts 4 and 5, respectively. The incidence of rash was more frequent with the combination treatment than with individual agents. The researchers reported two immune-related deaths due to Miller Fisher syndrome and myasthenia gravis in cohort 4.

Disclosure: For full disclosures of the study authors, visit

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