Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: Results from an open-label, multicenter phase i/ii study

S. F. Slovin, C. S. Higano, O. Hamid, S. Tejwani, A. Harzstark, J. J. Alumkal, H. I. Scher, K. Chin, P. Gagnier, M. B. McHenry, T. M. Beer

Research output: Contribution to journalArticlepeer-review

409 Scopus citations

Abstract

Background: This phase I/II study in patients with metastatic castration-resistant prostate cancer (mCRPC) explored ipilimumab as monotherapy and in combination with radiotherapy, based on the preclinical evidence of synergistic antitumor activity between anti-CTLA-4 antibody and radiotherapy. Patients and methods: In dose escalation, 33 patients (=6/cohort) received ipilimumab every 3 weeks × 4 doses at 3, 5, or 10 mg/kg or at 3 or 10 mg/kg + radiotherapy (8 Gy/lesion). The 10-mg/kg cohorts were expanded to 50 patients (ipilimumab monotherapy, 16; ipilimumab + radiotherapy, 34). Evaluations included adverse events (AEs), prostate-specific antigen (PSA) decline, and tumor response. Results: Common immune-related AEs (irAEs) among the 50 patients receiving 10 mg/kg ± radiotherapy were diarrhea (54%), colitis (22%), rash (32%), and pruritus (20%); grade 3/4 irAEs included colitis (16%) and hepatitis (10%). One treatment-related death (5 mg/kg group) occurred. Among patients receiving 10 mg/kg ± radiotherapy, eight had PSA declines of =50% (duration: 3-13+ months), one had complete response (duration: 11.3+ months), and six had stable disease (duration: 2.8-6.1 months). Conclusions: In mCRPC patients, ipilimumab 10 mg/kg ± radiotherapy suggested clinical antitumor activity with disease control and manageable AEs. Two phase III trials in mCRPC patients evaluating ipilimumab 10 mg/ kg ± radiotherapy are ongoing. ClinicalTrials.gov identifier: NCT00323882.

Original languageEnglish (US)
Article numbermdt107
Pages (from-to)1813-1821
Number of pages9
JournalAnnals of Oncology
Volume24
Issue number7
DOIs
StatePublished - Jul 2013

Keywords

  • Immunotherapy
  • Ipilimumab
  • Metastatic castration-resistant prostate cancer
  • Phase I/II trial
  • Prostate-specific antigen andradiotherapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

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