A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Comparing the Tolerability and Efficacy of Ipilimumab Administered with or without Prophylactic Budesonide in Patients with Unresectable Stage III or IV Melanoma

Clinical Cancer Research - Tập 15 Số 17 - Trang 5591-5598 - 2009
Jeffrey S. Weber1, John A. Thompson1, Omid Hamid1, David R. Minor1, Asim Amin1, Ilan G. Ron1, Ruggero Ridolfi1, Hazem Assi1, Anthony Maraveyas1, David M. Berman1,2, Jonathan Siegel1,2, Steven O’Day1
1Authors' Affiliations: 1Moffitt Cancer Center, Tampa, Florida; 2Seattle Cancer Care Alliance, University of Washington, Seattle, Washington; 3The Angeles Clinic and Research Institute, Santa Monica, California; 4California Pacific Medical Center, San Francisco Oncology Associates, San Francisco, California; 5Blumenthal Cancer Center, Charlotte, North Carolina; 6Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 7Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; 8Department of Internal Medicine, The Moncton Hospital, Moncton, New Brunswick, Canada; 9Castle Hill Hospital, Hull, United Kingdom; and 10Bristol-Myers Squibb, Lawrenceville, New Jersey
2BRISTOL MYERS-SQUIBB

Tóm tắt

Abstract Purpose: Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated with ipilimumab. A randomized, double-blind, placebo-controlled, multicenter, multinational phase II trial was conducted to determine whether prophylactic budesonide (Entocort EC), a nonabsorbed oral steroid, reduced the rate of grade ≥2 diarrhea in ipilimumab-treated patients with advanced melanoma. Experimental Design: Previously treated and treatment-naïve patients (N = 115) with unresectable stage III or IV melanoma received open-label ipilimumab (10 mg/kg every 3 weeks for four doses) with daily blinded budesonide (group A) or placebo (group B) through week 16. The first scheduled tumor evaluation was at week 12; eligible patients received maintenance treatment starting at week 24. Diarrhea was assessed using Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Patients kept a diary describing their bowel habits. Results: Budesonide did not affect the rate of grade ≥2 diarrhea, which occurred in 32.7% and 35.0% of patients in groups A and B, respectively. There were no bowel perforations or treatment-related deaths. Best overall response rates were 12.1% in group A and 15.8% in group B, with a median overall survival of 17.7 and 19.3 months, respectively. Within each group, the disease control rate was higher in patients with grade 3 to 4 irAEs than in patients with grade 0 to 2 irAEs, although many patients with grade 1 to 2 irAEs experienced clinical benefit. Novel patterns of response to ipilimumab were observed. Conclusions: Ipilimumab shows activity in advanced melanoma, with encouraging survival and manageable adverse events. Budesonide should not be used prophylactically for grade ≥2 diarrhea associated with ipilimumab therapy. (Clin Cancer Res 2009;15(17):5591–8)

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Clinical Cancer Research

Tập 15 Số 17

5591-5598

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