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

Background

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.

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.

Results

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 (7^th 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).

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

MELBASE database.

Funding

INCa, Roche, BMS, Novartis, MSD, Amgen.

Disclosure

L. Mortier: Financial Interests, Personal, Advisory Board: BMS, MSD, Pierre Fabre, Novartis, Sanofi. H. Montaudie: Financial Interests, Personal, Research Funding: BMS, Merck, MSD, Novartis, Pierre Fabre, Leo pharma, Checkpoint Therapeutic, Huyaboiscience, Incyte, Nektar Pharmaceutical, Regeneron, Replimune; Financial Interests, Personal, Funding: BMS, Merck Serono, MSD Novartis, Pierre Fabre; Financial Interests, Institutional, Advisory Board: BMS, Leo Pharma. C. Pages: Financial Interests, Personal, Advisory Board: BMS. C. Lebbe: Financial Interests, Personal, Funding: Roche, BMS, Novartis, Amgen, MSD, Pierre Fabre, Pfizer, Incyte; Financial Interests, Personal, Advisory Role: BMS, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche, BMS, Novartis, Amgen, MSD; Financial Interests, Institutional, Research Funding: Roche, BMS, Novartis, Amgen, MSD; Financial Interests, Personal, Advisory Board: Avantis Medical Systems, InflaRx, Sanofi, BMS, MSD, Pierre Fabre, Novartis, Jazz Pharmaceuticals; Financial Interests, Personal, Other: BMS, MSD, Novartis, Sanofi, Pierre Fabre. All other authors have declared no conflicts of interest.