Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

Tomasz M Beer, Eugene D Kwon, Charles G Drake, Karim Fizazi, Christopher Logothetis, Gwenaelle Gravis, Vinod Ganju, Jonathan Polikoff, Fred Saad, Piotr Humanski, Josep M Piulats, Pablo Gonzalez Mella, Siobhan S Ng, Dirk Jaeger, Francis X Parnis, Fabio A Franke, Javier Puente, Roman Carvajal, Lisa Sengeløv, M Brent McHenryArvind Varma, Alfonsus J van den Eertwegh, Winald Gerritsen, Laura Ridolfi

Research output: Contribution to journalArticle

Abstract

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

Original languageEnglish
Pages (from-to)40-47
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number1
DOIs
Publication statusPublished - Jan 2017

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Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Asymptomatic Diseases
  • Bone Neoplasms
  • Diarrhea
  • Disease-Free Survival
  • Double-Blind Method
  • Humans
  • Ipilimumab
  • Male
  • Middle Aged
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant
  • Survival Rate
  • Clinical Trial, Phase III
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial

Cite this

Beer, T. M., Kwon, E. D., Drake, C. G., Fizazi, K., Logothetis, C., Gravis, G., Ganju, V., Polikoff, J., Saad, F., Humanski, P., Piulats, J. M., Gonzalez Mella, P., Ng, S. S., Jaeger, D., Parnis, F. X., Franke, F. A., Puente, J., Carvajal, R., Sengeløv, L., ... Ridolfi, L. (2017). Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer. Journal of Clinical Oncology, 35(1), 40-47. https://doi.org/10.1200/JCO.2016.69.1584