Nivolumab ( Opdivo ) is a programmed death-1 ( PD-1 ) immune checkpoint inhibitor which has shown durable tumor responses in multiple cancer types and prolongs overall survival in patients with melanoma.
The objective of the current analysis is to describe the safety profile of Nivolumab across recent melanoma studies, including 4 studies in which guidelines for the management of adverse events ( AEs ) were utilized.
A retrospective safety review was conducted for 4 ongoing phase I–III trials, in which patients with melanoma received Nivolumab 3 mg/kg Q2W ( every 2 weeks ) until disease progression or unacceptable toxicity.
Data were included from patients who received at least 1 dose of Nivolumab, and included assessments of adverse effects, select adverse reactions ( immune-related etiology ), time to onset and resolution, and the use as well as impact of immunemodulating agents ( IMs ).
A total of 576 patients received Nivolumab for a median of 3.7 months; 312 ( 54% ) had received prior Ipilimumab ( Yervoy ).
The most frequent drug-related adverse reactions of any grade were fatigue ( 25% ), pruritus ( 17% ), diarrhea ( 13% ), and rash ( 13% ); grade 3–4 drug-related adverse effects occurred in 10% of all patients, and in 8% of patients with prior Ipilimumab.
No drug-related deaths were reported.
Drug-related select adverse effects of any grade were most frequent in the skin ( 34% ), gastrointestinal tract ( 13% ), endocrine glands ( 8% ) and liver ( 4% ); grade 3–4 select adverse effects occurred in 4% of patients.
Median time to onset of drug-related select adverse effects ranged from 5 wks for skin adverse effects to 15 weeks for renal adverse effects.
Immunemodulating agents were administered to 166/474 patients ( 35% ) in phase III studies to manage adverse effects; 114 patients ( 24% ) received systemic corticosteroids.
Among 21 patients with grade 3–4 drug-related select adverse effects, all but 1 patient with a skin adverse reaction resolved with immunemodulating agents.
Median time to resolution ranged from 3 weeks for hepatic adverse effects to 29 weeks for skin adverse reactions.
The objective response rate was 44% in patients who received an immunemodulating agent and 36% in those who did not; time to response was similar ( median 9 weeks ), and the median duration of response was not reached for either patient subgroup.
In conclusion, in this pooled analysis, drug-related adverse effects with Nivolumab monotherapy were primarily low grade and the incidence of grade 3–4 drug-related adverse effects was not affected by prior Ipilumumab.
Nearly all drug-related grade 3–4 select adverse effects resolved with use of immunemodulating agents, which did not appear to impact on tumor response. ( Xagena )
Weber JS et al, J Clin Oncol 33, 2015 (suppl; abstr 9018)