Improved survival with ipilimumab in patients with metastatic melanoma Journal Article
| Authors: | Hodi, F. S.; O'Day, S. J.; McDermott, D. F.; Weber, R. W.; Sosman, J. A.; Haanen, J. B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J. C.; Akerley, W.; Van Den Eertwegh, A. J. M.; Lutzky, J.; Lorigan, P.; Vaubel, J. M.; Linette, G. P.; Hogg, D.; Ottensmeier, C. H.; Lebbé, C.; Peschel, C.; Quirt, I.; Clark, J. I.; Wolchok, J. D.; Weber, J. S.; Tian, J.; Yellin, M. J.; Nichol, G. M.; Hoos, A.; Urba, W. J. |
| Article Title: | Improved survival with ipilimumab in patients with metastatic melanoma |
| Abstract: | Background: An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab - which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response - administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. Methods: A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. Results: The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Conclusions: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.) Copyright © 2010 Massachusetts Medical Society. |
| Keywords: | adult; cancer survival; controlled study; treatment outcome; treatment response; aged; middle aged; major clinical study; overall survival; clinical trial; constipation; hepatitis; cancer growth; diarrhea; side effect; cancer patient; combined modality therapy; temozolomide; cancer staging; anorexia; carboplatin; dacarbazine; glycoprotein gp 100; interleukin 2; ipilimumab; melanoma; controlled clinical trial; pain; anemia; skin neoplasms; randomized controlled trial; vomiting; body weight; cancer mortality; abdominal pain; alanine aminotransferase blood level; aspartate aminotransferase blood level; coughing; drug fever; injection site reaction; pruritus; rash; kaplan-meiers estimate; alanine aminotransferase; aspartate aminotransferase; drug induced headache; antibodies, monoclonal; cancer vaccines; cytotoxic t lymphocyte; cancer fatigue; colitis; hazard ratio; phase 3 clinical trial; antigens, cd; hypothyroidism; peptide vaccine; corticosteroid; cytotoxic t lymphocyte antigen 4; hla a antigen; double blind procedure; double-blind method; leukocytosis; thyrotropin; fotemustine; metastatic melanoma; adrenal insufficiency; central nervous system metastasis; corticotropin; corticotropin blood level; hypophysitis; hypopituitarism; proctocolitis; rectal pain; thyrotropin blood level; vitiligo |
| Journal Title: | New England Journal of Medicine |
| Volume: | 363 |
| Issue: | 8 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2010-08-19 |
| Start Page: | 711 |
| End Page: | 723 |
| Language: | English |
| DOI: | 10.1056/NEJMoa1003466 |
| PUBMED: | 20525992 |
| PROVIDER: | scopus |
| PMCID: | PMC3549297 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 110" - "Export Date: 20 April 2011" - "CODEN: NEJMA" - "Source: Scopus" |
