Efficacy of nivolumab four-weekly dosing schedule based on body weight

Abstract

Nivolumab has received regulatory approval to be given by weight-based or flat dosing every two weeks or by flat dosing every four weeks. However, flat dosing would lead to unnecessarily high doses for patients with lower body weight, increasing the drug usage and probability of toxicity. We review the rationale of using a four-weekly hybrid dosing strategy using weight-based and flat-dosing regimens adopted by some jurisdictions.

Dosing of PD-1 and PD-L1 inhibitors: Cost saving initiatives for significantly decreasing associated expenditure

“…5 This equates to a dose of 6 mg/kg and can be supported by the serum levels estimated from pharmacokinetic modelling studies and the known pharmacokinetic parameters. 20 For patients weighing greater than 80 kg, flat dosing will generate significant cost savings above BW-based dosing. However, in patients weighing less than 80 kg, the reverse will be true.…”

Structure and Optimization of Checkpoint Inhibitors

“…Peripheral PD-1 receptor occupancy is saturated at doses ≥ 0.3 mg/kg after eight weeks treatment, again supporting minimizing the doses administered, although the degree of intra-tumoral receptor occupancy is not yet known [66]. Some regulatory authorities have suggested weight-based dosing for patients less than 80 kg and fixed dosing above, to avoid unnecessarily high doses for lower-weight patients [67]. Avelumab is currently approved at a weight-based dosing of 10 mg/kg, but simulations suggested that similar risk/benefit profiles would result from fixed dosing at 800 mg, leading to FDA approval of this fixed dose [68].…”

Economic sustainability of nivolumab at flat dose for second-line treatment of metastatic non-small cell lung cancer in real life

“…Subsequently, nivolumab was approved at 240 mg flat dose Q2W. 4 Recently, de Lemos et al 5 have reviewed the rationale of using a four-weekly (Q4W) hybrid dosing strategy using weight-based and flat-dosing regimens, remarking the rationale of flat dosing. However, these improvements come along with a dramatic increase of drug's costs.…”

“…At the last FUT, three patients (33.3%) were deceased and six patients (66.7%) were alive with metastases. Median OS was 13.98 months (range: 8.62-23.09 months), with a mean of nine cycles of nivolumab for patient (range: [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. No serious (!3) adverse events were reported.…”