Background: Nivolumab (Opdivo) was initially FDAapproved at a dose of 3mg/kg by intravenous infusion over 60 minutes every 2 weeks. In September 2016, nivolumab’s FDA approved dosing was changed from 3mg/kg to a 240mg flat dose. In January 2018, nivolumab’s FDA approved dosing was updated to reflect a decreased infusion time of 30 minutes. In March 2018, nivolumab’s FDA approved dosing was again modified from 240mg every 2 weeks to 480mg every 4 weeks. The VA Northeast Ohio Healthcare System (VANEOHS) adopted the 480mg every 4 weeks regimen in March 2018. The increased nivolumab dose and shortened infusion time raised some concern regarding immune-mediated toxicities which was the rationale behind this medication use evaluation (MUE).
Methods: This retrospective chart review was completed to compare the incidence of toxicity between the every 2 week and the every 4 week dosing schedules and evaluate the adoption of every 4 week dosing regimen by VANEOHS prescribers. Patients newly initiated on nivolumab between 10/1/17 and 9/30/18 were reviewed for the occurrence of immune-mediated adverse events (AEs) within the first 3 months of treatment.
Results: Sixty-five patients were included in the MUE, with 21 (46%) initiated on 240mg every 2 weeks and 25 (54%) initiated on 480mg every 4 weeks. All patients initiated on 240mg every 2 weeks were either converted to 480mg every 4 weeks, or nivolumab therapy was discontinued prior to VANEOHS adoption of the 4 week dosing regimen. Immune-mediated AEs potentially related to nivolumab therapy were documented in 8 (32%) patients receiving 480mg, and 4 (36%) patients receiving 240mg. Of patients who switched from nivolumab 240mg to 480mg, 3 (30%) experienced an AE while receiving 240mg, and 1 (10%) while receiving 480mg.
Conclusion: The nivolumab 480mg every 4 week dosing regimen was readily adopted by oncology providers at VANEOHS and the rate of patients experiencing AEs with nivolumab 480mg every 4 weeks compared to 240mg every 2 weeks, was similar between treatment groups. The results of this MUE support continued prescribing of the nivolumab 480mg every 4 week dosing regimen with close monitoring for adverse reactions.
