Study Details Adverse Events in Pivotal Ipilimumab Trial

Ben Leach
Published: Friday, Aug 16, 2013
Dr. Jeffrey S. Weber
Jeffrey S. Weber, MD, PhD

Director, Donald A. Adam Comprehensive Melanoma Research Center, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Moffitt Cancer Center
Adverse events (AEs) associated with ipilimumab (Yevoy) for the treatment of metastatic melanoma are better understood after further analysis of clinical trial data that led to the FDA’s 2011 approval of the drug, including when those AEs are likely to manifest and the best methods of managing them.

The results of the analysis confirm that “careful follow-up and early intervention,” coupled with guidelines-based management of immune-related adverse events (irAEs), are vital components of treating patients with the immunotherapy agent, according to the analysis published in Cancer.1 Concomitant medications were given frequently to patients treated during the study (Table).

Jeffrey S. Weber, MD, PhD, of the H. Lee Moffitt Cancer Center and Research Institute in Florida, and others set out to look at the pivotal clinical trial data once again to determine the patterns and development of these AEs.

Weber and colleagues used data from the phase III MDX010-20 trial, in which 676 previously treated patients with metastatic melanoma were randomized 3:1:1 to receive ipilimumab 3 mg/kg plus the glycoprotein 100 melanoma antigen vaccine (gp100), ipilimumab 3 mg/kg plus placebo, or the gp100 vaccine plus placebo.

In the entire clinical trial population, 14 deaths appear related to the study drugs, including seven deaths associated with irAEs. For ipilimumab monotherapy, the irAEs consisted of one case each of bowel perforation and liver failure. Among those treated with ipilimumab plus gp100, deaths related to irAEs included three patients with bowel perforation/inflammatory colitis, bowel perforation, or multiorgan failure/peritonitis; and one case each of colitis and septicemia, and Guillain-Barré syndrome.

The most frequently reported irAEs affected the skin and gastrointestinal (GI) tract, and most of the patients who died as a result of irAEs experienced GI events, notably colitis. However, Weber et al noted that, “There is no evidence that bowel involvement in patients with melanoma increases the likelihood that colitis, especially dose-limiting colitis, will occur after receiving ipilimumab.”

Table. Selected Concomitant Medications Used by ≥10% of Patients in MDX010-20 Trial1

Percentage of Patients
Medication Ipilimumab Alone
(n = 131)
Ipilimumab Plus gp100
(n = 380)
gp100
(n = 132)
Analgesics 68.7 72.4 78
Drugs for acid-related disorders 43.5 45.3 46.2
Psycholeptics 41.2 41.3 44.7
Antibacterial for systemic use 35.9 38.9 30.3
Antihistamines for systemic use 33.6 36.1 26.5
Anti-inflammatory and antirheumatic products 37.4 35.8 38.6
Corticosteroids for systemic use 35.1 34.5 25
Psychoanaleptics 29 28.7 27.3
Antithrombotic agents 33.6 25.8 36.4
Drugs for functional gastrointestinal disorders 23.7 22.1 27.3



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