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| |  Response to Investigational Ipilimumab Observed Among Patients With Advanced Melanoma: Presented at ASCO By Ed Susman CHICAGO -- June 5, 2008 -- More than one-quarter of patients with advanced melanoma attained clinical benefit when they were treated with the investigational agent ipilimumab, researchers said at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting. "We think that treatment with ipilimumab gives patients hope that we really have a new treatment that works," said Steven O'Day, MD, Angeles Clinic and Research Institute, Santa Monica, California. Ipilimumab is a fully human, monoclonal antibody directed against CTLA-4, a key negative regulator of T-cell response to tumour-associated antigens. Dr. O'Day said the drug has been used in treating more than 500 patients with advanced melanoma. Phase 3 trials of first-line ipilimumab with or without chemotherapy in patients with melanoma are now underway. In their open-label, multicentre study, Dr. O'Day and colleagues enrolled 155 patients with advanced, unresectable, stage III or IV, malignant melanoma. The average age of patients was 59 years, and 52% were men. About 5.8% of the patients achieved responses and about 27.1% attained disease control. Median overall survival was 10.2 months, and 1-year survival was 46.7%, Dr. O'Day said in his oral presentation on June 2. Patients received ipilimumab induction dosing at 10 mg/kg every third week for 4 cycles and then received maintenance dosing every 12 weeks beginning at week 24. Grade 3 or 4 immune-related adverse events were reported in 21.9% of patients; gastrointestinal side effects were the most common adverse event in 8.4% of patients. These immune overactivation effects correlated highly with long-term survival, Dr. O'Day commented. He noted that these results were "remarkably consistent" with 2 other pivotal ipilimumab trials reported at this meeting, all showing ipilimumab treatment stopped tumour growth in about 30% of patients in the first 12 weeks, followed by tumour shrinkage. Another 10% to 20% of patients progressed early and then developed late responses. "With immunotherapy, best overall response rate does not appear to capture ipilimumab activity fully, so overall survival should be used instead, to evaluate the drug's efficacy," Dr. O'Day said. "With immunotherapy you have to 'build up your army,' which takes about 12 to 24 weeks. So it's important to recognise that survival is the most important endpoint and that early progression does not mean that patients are not going to benefit." He noted also that in about 30% of patients there is a plateau effect such that long-term survival has been anywhere from 10 to 15 months, as compared with 6 to 9 months typically for high-dose interleukin 2 (IL-2). While ipilimumab is given as an outpatient treatment, IL-2 is given in hospital or often in the ICU because of its acute side effects, which do not correlate with better outcome, Dr. O'Day said. Funding for this study was provided by Bristol-Myers Squibb and Medarex.
[Presentation title: Efficacy and Safety of Ipilimumab Induction and Maintenance Dosing in Patients With Advanced Melanoma Who Progressed on One or More Prior Therapies. Abstract 9021]
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