Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma

Abstract

Purpose We conducted a retrospective analysis to assess the safety profile of nivolumab monotherapy in patients with advanced melanoma and describe the management of adverse events (AEs) using established safety guidelines. Patients and Methods Safety data were pooled from four studies, including two phase III trials, with patients who received nivolumab 3 mg/kg once every 2 weeks. We evaluated rate of treatment-related AEs, time to onset and resolution of select AEs (those with potential immunologic etiology), and impact of select AEs and suppressive immune-modulating agents (IMs) on antitumor efficacy. Results Among 576 patients, 71% (95% CI, 67% to 75%) experienced any-grade treatment-related AEs (most commonly fatigue [25%], pruritus [17%], diarrhea [13%], and rash [13%]), and 10% (95% CI, 8% to 13%) experienced grade 3 to 4 treatment-related AEs. No drug-related deaths were reported. Select AEs (occurring in 49% of patients) were most frequently skin related, GI, endocrine, and hepatic; grade 3 to 4 select AEs occurred in 4% of patients. Median time to onset of select AEs ranged from 5 weeks for skin to 15 weeks for renal AEs. Approximately 24% of patients received systemic IMs to manage select AEs, which in most cases resolved. Adjusting for number of doses, objective response rate (ORR) was significantly higher in patients who experienced treatment-related select AEs of any grade compared with those who did not. ORRs were similar in patients who did and patients who did not receive systemic IMs. Conclusion Treatment-related AEs with nivolumab monotherapy were primarily low grade, and most resolved with established safety guidelines. Use of IMs did not affect ORR, although treatment-related select AEs of any grade were associated with higher ORR, but no progression-free survival benefit.

Enterocolitis due to immune checkpoint inhibitors: a systematic review

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Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

“…Although recent analyses on cumulative toxicity associated with ICBs after long-term therapy are needed, an analysis conducted in 306 patients with advanced solid tumors treated for up to 22 months with nivolumab monotherapy in a phase 1 study showed no cumulative toxicity after a minimum of 14 months of follow-up [148]. In a pooled safety analysis of 282 patients with advanced melanoma who were treated with nivolumab monotherapy in two phase 3 and two phase 1 studies and who experienced new treatment-related imAEs, 85% did so within the first 16 weeks of treatment [149]. Based on a long-term safety analysis conducted in 95 patients with metastatic UC treated with atezolizumab in a phase 1a trial, most treatment-related AEs occurred within the first year after treatment initiation, with a 50% reduction in the incidence of these AEs during the second year [150].…”