In a retrospective study reported in the Journal of Clinical Oncology, Sznol et al have provided a pooled safety profile of combination nivolumab (Opdivo) and ipilimumab (Yervoy) treatment in patients with advanced melanoma.
The study included data from 448 patients from a phase Ib trial (n = 41), the phase II CheckMate 069 trial (n = 94), and the phase III CheckMate 067 trial (n = 313). Patients received at least one dose of nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg every 3 weeks for a planned 4 cycles and then nivolumab at 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity, with established guidelines for adverse event management being followed.
Adverse Event Profile
Median duration of follow-up was 13.2 months. Treatment-related grade 3 or 4 adverse events occurred in 55.5% of patients, and treatment-related adverse events of any grade led to discontinuation of treatment in 35.7%. The most common treatment-related immune-related adverse events of any grade were skin events (64.3%) and gastrointestinal (GI) events (46.7%); the most common grade 3 or 4 events were hepatic events (17.0%) and GI events (16.3%). Overall, 30.1% of patients had a grade 2 to 4 immune-related adverse event in more than one organ category.
Median time to onset of grade 3 or 4 treatment-related immune-related adverse events ranged from 3.1 weeks (skin) to 16.3 weeks (renal). Median time to resolution, excluding endocrinopathies, ranged from 1.9 weeks (renal) to 4.5 weeks (pulmonary), with resolution rates ranging from 79% to 100% with the use of immune-modulating agents. Endocrinopathies frequently required long-term hormone replacement therapy. Four patients died due to treatment-related adverse events.
The investigators concluded: “Frequency of grade 3/4 treatment-related [adverse events] was higher with nivolumab plus ipilimumab and occurred earlier than historical experience with either agent alone, but resolution rates were similar.”
The study was supported by Bristol-Myers Squibb.
Mario Sznol, MD, of the Yale Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
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