title: Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study.
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.
  
  
  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.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York. Electronic address: slovins@mskcc.org.
authors.forename: S F
authors.initials: SF
authors.lastname: Slovin
authors.affiliation: Department of Medicine, Seattle Cancer Care Alliance, University of Washington, Seattle.
authors.forename: C S
authors.initials: CS
authors.lastname: Higano
authors.affiliation: Department of Translational Research/Immunotherapy, The Angeles Clinic and Research Institute, Santa Monica.
authors.forename: O
authors.initials: O
authors.lastname: Hamid
authors.affiliation: Department of Hematology-Oncology, Henry Ford Health System, Detroit.
authors.forename: S
authors.initials: S
authors.lastname: Tejwani
authors.affiliation: Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.
authors.forename: A
authors.initials: A
authors.lastname: Harzstark
authors.affiliation: Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland.
authors.forename: J J
authors.initials: JJ
authors.lastname: Alumkal
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York.
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Department of Oncology Global Clinical Research, Bristol-Myers Squibb, Wallingford, USA.
authors.forename: K
authors.initials: K
authors.lastname: Chin
authors.affiliation: Department of Oncology Global Clinical Research, Bristol-Myers Squibb, Wallingford, USA.
authors.forename: P
authors.initials: P
authors.lastname: Gagnier
authors.affiliation: Department of Oncology Global Clinical Research, Bristol-Myers Squibb, Wallingford, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: McHenry
authors.affiliation: Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland.
authors.forename: T M
authors.initials: TM
authors.lastname: Beer
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D017430:Prostate-Specific Antigen
keywords: immunotherapy; ipilimumab; metastatic castration-resistant prostate cancer; phase I/II trial; prostate-specific antigen and radiotherapy
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