S J O'Day1, M Maio2, V Chiarion-Sileni3, T F Gajewski4, H Pehamberger5, I N Bondarenko6, P Queirolo7, L Lundgren8, S Mikhailov9, L Roman10, C Verschraegen11, R Humphrey12, R Ibrahim12, V de Pril13, A Hoos12, J D Wolchok14. 1. The Angeles Clinic and Research Institute, Santa Monica, CA, USA. Electronic address: SODay@theangelesclinic.org. 2. Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena. 3. Department of Melanoma and Skin Cancer Unit, IOV-IRCCS, Padua, Italy. 4. Department of Pathology; Department of Medicine, University of Chicago, Chicago, IL, USA. 5. Department of Dermatology, Medical University of Vienna, Vienna, Austria. 6. Dnepropetrovsk State Medical Academy, Dnepropetrovsk, Ukraine. 7. Department of Medical Oncology A, National Institute for Cancer Research, Genova, Italy. 8. Department of Oncology, Lund University Hospital, Lund, Sweden. 9. Stavropol Regional Clinical Oncology Center, Stavropol. 10. Leningrad Regional Oncology Center, St Petersburg, Russian Federation. 11. University of New Mexico Cancer Center, Albuquerque, NM. 12. Bristol-Myers Squibb Company, Wallingford, CT, USA. 13. Bristol-Myers Squibb Company, Braine-l'Alleud, Belgium. 14. Department of Medicine and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Abstract
BACKGROUND: This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma. PATIENTS AND METHODS: Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC). RESULTS: BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One- and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids. CONCLUSION: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.
BACKGROUND: This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma. PATIENTS AND METHODS: Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC). RESULTS: BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One- and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids. CONCLUSION:Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.
Authors: Lidia Robert; Jennifer Tsoi; Xiaoyan Wang; Ryan Emerson; Blanca Homet; Thinle Chodon; Stephen Mok; Rong Rong Huang; Alistair J Cochran; Begoña Comin-Anduix; Richard C Koya; Thomas G Graeber; Harlan Robins; Antoni Ribas Journal: Clin Cancer Res Date: 2014-02-28 Impact factor: 12.531