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.

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 >or=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 >or=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 >or=2 diarrhea associated with ipilimumab therapy.

• Authors: Jeffrey Weber, John A Thompson, Omid Hamid, David Minor, Asim Amin, Ilan Ron, Ruggero Ridolfi, Hazem Assi, Anthony Maraveyas, David Berman, Jonathan Siegel, Steven J O'Day
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 17 Pg. 5591-8 (Sep 01 2009) ISSN: 1557-3265 [Electronic] United States
• PMID: 19671877 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• Ipilimumab
• Budesonide

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents (administration & dosage)
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols
• Budesonide (administration & dosage)
• Diarrhea (chemically induced, drug therapy)
• Double-Blind Method
• Female
• Humans
• Ipilimumab
• Kaplan-Meier Estimate
• Male
• Melanoma (drug therapy, pathology)
• Middle Aged
• Neoplasm Staging
• Skin Neoplasms (drug therapy, pathology)
• Treatment Outcome