1160P Methods of nivolumab administration in advanced melanoma: A comparison of patients’ clinical outcomes treated with flat dose or weight-adjusted dose, FLATIMEL study

Nivolumab obtained marketing authorization in advanced melanoma (AM) with weight-adjusted (WA) dose administration (3 mg/kg/2 weeks) 1. Based on modeling studies (no clinical data), EMA advised in 2018 that nivolumab should be administered in flat dose regimen (240 mg/2 weeks or 480 mg/4 weeks) 2 3. The aim of the FLATIMEL study was to compare clinical outcomes of AM patients treated with both nivolumab dose calculation methods. AM patients were prospectively included in the national multicenter MelBase database since 2013 (NCT02828202). Patients treated by nivolumab monotherapy in first line enrolled in MelBase were included in our study. We compared safety and efficacy of nivolumab in 2 groups of patients treated by flat or WA dose. The primary endpoint was the incidence of immune-related adverse events (irAEs) of grade ≥ 3. Secondary endpoints were incidence of irAEs of any grade, overall survival (OS) and progression free survival (PFS). Inverse probability of treatment weighting was used to balance groups on their baseline characteristics. Between June 2015 and January 2022, 546 patients followed in MelBase were included in this study: 252 in the flat dose group and 294 in the WA group. Patients with metastatic organs ≥ 3 (p<0.0001), brain metastasis (p=0.0005) or M1c AJCC (7th edition) tumor stage (p=0.001) were more frequent in the WA group. After weighting, no difference between both groups was observed for irAEs grade ≥ 3 (n=65, 12%), (p= 0.51), whereas irAEs of any grade (n=314, 57.5%) were more frequent in the flat dose group (p=0.044), especially muco-cutaneous and endocrine toxicities. Median OS was 32.3 and 20.6 months in flat dose and WA group respectively (p= 0.004), and median PFS was 3.5 and 2.8 months, respectively (p= 0.003). There was no difference in the incidence of severe irAEs between AM patients treated by WA or flat dose of Nivolumab. Survival results were superior in the flat dose group, which may be explained by a temporal bias. Cost effectiveness studies are necessary.