Pembrolizumab for advanced prostate adenocarcinoma: Findings of the KEYNOTE-028 study

A. R. Hansen, C. Massard, P. A. Ott, N. B. Haas, J. S. Lopez, S. Ejadi, J. M. Wallmark, B. Keam, J. P. Delord, R. Aggarwal, M. Gould, P. Yang, S. M. Keefe, S. A. Piha-Paul

Research output: Contribution to journalArticle

52 Scopus citations


Background: Patients with castration-resistant prostate cancer derive only modest clinical benefit from available therapies. Blockade of the inhibitory programmed death 1 (PD-1) receptor by monoclonal antibodies has been effective in several Malignancies. Results from the prostate adenocarcinoma cohort of the nonrandomized phase Ib KEYNOTE-028 trial of pembrolizumab in advanced solid tumors are presented. Materials and methods: Key eligibility criteria included advanced prostate adenocarcinoma, unsuccessful standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and PD-1 ligand (PD-L1) expression in 1% of tumor or stromal cells. Patients received pembrolizumab 10 mg/kg every 2 weeks until disease progression or intolerable toxicity for up to 24 months. Primary end point was objective response rate (ORR) per RECIST v1.1 by investigator review. Results: Median patient age in this cohort (n ¼ 23) was 65 years; 73.9% of patients received at Least two prior therapies for metastatic disease. There were four confirmed partial responses, for an ORR of 17.4% [95% confidence interval (CI) 5.0%–38.8%]; 8 of 23 (34.8%) patients had stable disease. Median duration of response was 13.5 months. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9 months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, respectively. One patient remained on treatment at data cutoff. After a median follow-up of 7.9 months, 14 (60.9%) patients experienced treatment-related adverse events (TRAEs), most commonly nausea (n ¼ 3, 13.0%). Four (17.3%) experienced grade 3/4 TRAEs: grade 3 peripheral neuropathy, grade 3 asthenia, grade 3 fatigue, and grade 4 lipase increase. No pembrolizumab-related deaths or discontinuations occurred. Conclusion: Pembrolizumab resulted in durable objective response in a subset of patients with heavily pretreated, advanced PD-L1–positive prostate cancer, and its side effect profile was favorable.

Original languageEnglish
Pages (from-to)1807-1813
Number of pages7
JournalAnnals of Oncology
Issue number8
StatePublished - 1 Jan 2018



  • Castration-resistant prostate cancer
  • PD-1
  • PD-L1
  • Pembrolizumab

Cite this

Hansen, A. R., Massard, C., Ott, P. A., Haas, N. B., Lopez, J. S., Ejadi, S., Wallmark, J. M., Keam, B., Delord, J. P., Aggarwal, R., Gould, M., Yang, P., Keefe, S. M., & Piha-Paul, S. A. (2018). Pembrolizumab for advanced prostate adenocarcinoma: Findings of the KEYNOTE-028 study. Annals of Oncology, 29(8), 1807-1813.