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

   

Authors:	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.
Article 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. 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. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Keywords:	adult; cancer survival; controlled study; treatment response; aged; major clinical study; fatigue; hepatitis; cancer growth; diarrhea; monotherapy; side effect; treatment duration; cancer radiotherapy; radiation dose; prostate specific antigen; cytotoxic t lymphocyte antigen 4 antibody; ipilimumab; cancer immunotherapy; multiple cycle treatment; phase 2 clinical trial; nausea; vomiting; hemoglobin; antineoplastic activity; docetaxel; drug dose escalation; lymphocytopenia; pneumonia; pruritus; rash; goserelin; leuprorelin; alkaline phosphatase; cause of death; drug fatality; immunotherapy; heart infarction; multicenter study; sepsis; colitis; liver disease; disease duration; metastasis potential; intestine perforation; external beam radiotherapy; maximum tolerated dose; phase 1 clinical trial; bicalutamide; flutamide; nilutamide; hyperthyroidism; hypothyroidism; levothyroxine; corticosteroid; granulocyte macrophage colony stimulating factor vaccine; mycophenolic acid 2 morpholinoethyl ester; neurologic disease; endocrine disease; aspergillosis; hormone substitution; phase i/ii trial; castration resistant prostate cancer; adrenal insufficiency; decreased appetite; abnormal laboratory result; hypophysitis; hypopituitarism; infliximab; metastatic castration-resistant prostate cancer; prostate-specific antigen andradiotherapy
Journal Title:	Annals of Oncology
Volume:	24
Issue:	7
ISSN:	0923-7534
Publisher:	Oxford University Press
Date Published:	2013-07-01
Start Page:	1813
End Page:	1821
Language:	English
DOI:	10.1093/annonc/mdt107
PROVIDER:	scopus
PMCID:	PMC3707423
PUBMED:	23535954
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84880508629&partnerID=40&md5=e7dc4041c56b4d0ca7489ac91294270c
Notes:	--- - Cited By (since 1996):3 - "Export Date: 2 December 2013" - "Art. No.: mdt107" - "CODEN: ANONE" - "Source: Scopus"

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