Analysis Supports Flat Dose of Nivolumab 480 mg Every 4 Weeks
A flat-dosing schedule of nivolumab (480 mg every 4 weeks) showed pharmacologic activity and safety similar to other schedules.
A flat-dosing schedule of nivolumab 480 mg every 4 weeks (Q4W) showed similar pharmacologic activity and safety across several cancer types compared with a more frequent weight-based (3 mg/kg) or a flat-dosing (240 mg) schedule every 2 weeks (Q2W).1 Earlier this year, nivolumab 480 mg Q4W was approved by the US Food and Drug Administration as an alternative dosing regimen for several cancer indications.2 The study was published online September 12, 2018, in the Annals of Oncology.
For the pharmacokinetics (PK) analysis, patient data were pooled from clinical trials evaluating nivolumab in patients across several cancer types: melanoma, renal cell carcinoma, non-small cell lung cancer, colorectal cancer, gastric cancer, and others. Using modeling and simulation, the PK analysis intended to compare the PK exposure of 480 mg Q4W with more frequent schedules, 3 mg/kg Q2W and 240 mg Q2W.
The safety data pool was made up of 61 patients from 4 ongoing phase 3 trials and intended to assess the safety of nivolumab 480 mg Q4W.
At steady state, nivolumab 480 mg Q4W had a time-averaged concentration similar to 3 mg/kg Q2W. Trough concentration was approximately 16% lower and peak concentration was approximately 45% higher for 480 mg Q4W compared to 3 mg/kg Q2W.
After transitioning from 3 mg/kg Q2W to 480 mg Q4W, 14.8% of patients reported treatment-related adverse events and 1.6% of patients reported grade 3 or grade 4 treatment-related adverse events. The safety data were consistent with what has been reported for 3 mg/kg Q2W schedules.
“In conclusion, nivolumab 480 mg Q4W is predicted to have a similar overall exposure and safety profile to 3 mg/kg Q2W and 240 mg Q2W dosing across patients with various tumor types,” the study authors wrote. “The 480 mg Q4W flat dose has the potential to be practice-changing and is expected to improve ease of administration, shorten patient waiting time, and reduce costs incurred by patients and cancer care institutions.”
Disclosure: This study was funded by a pharmaceutical company. For a complete list of disclosures, please refer to the original study.
- Long GV, Tykodi SS, Schneider JG, et al. Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer [published online September 12, 2018]. Ann Oncol. doi: 10.1093/annonc/mdy408
- Bristol-Myers Squibb's Opdivo® (nivolumab) now the first and only FDA-approved PD-1 inhibitor to offer every four-week dosing [news release]. Princeton, NJ: Bristol-Myers Squibb; March 6, 2018. https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibbs-opdivo-nivolumab-now-first-and-only-fda-. Accessed October 4, 2018.