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

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    348 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 1 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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    Slovin, S. F., Higano, C. S., Hamid, O., Tejwani, S., Harzstark, A., Alumkal, J. J., Scher, H. I., Chin, K., Gagnier, P., McHenry, M. B., & Beer, T. M. (2013). Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: Results from an open-label, multicenter phase i/ii study. Annals of Oncology, 24(7), 1813-1821. [mdt107]. https://doi.org/10.1093/annonc/mdt107