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Observational Study
. 2025 Jan 1;131(1):e35679.
doi: 10.1002/cncr.35679. Epub 2024 Dec 8.

Methods of nivolumab administration in advanced melanoma: A comparison of patients' clinical outcomes treated with flat dose or weight-adjusted dose, a multicenter observational study

Iona Campo Le Brun  1 , Séphane Dalle  2 , Laurent Mortier  3 , Olivier Dereure  4 , Sophie Dalac Rat  5 , Caroline Dutriaux  6 , Marie-Thérèse Leccia  7 , Delphine Legoupil  8 , Henri Montaudié  9 , Julie De Quatrebarbes  10 , Caroline Gaudy-Marqueste  11 , Eve Maubec  12 , Philippe Saiag  13 , Cécile Pagès  14 , Florence Brunet Possenti  15 , Florence Granel-Brocard  16 , Raphaël Porcher  17 , Wendy Lefevre  18 , Célèste Lebbé  19 , Emmanuelle Kempf  1
Affiliations
Observational Study

Methods of nivolumab administration in advanced melanoma: A comparison of patients' clinical outcomes treated with flat dose or weight-adjusted dose, a multicenter observational study

Iona Campo Le Brun et al. Cancer. .

Abstract

Background: Nivolumab obtained approval in advanced melanoma (AM) with weight-adjusted dose (WAD) administration (3 mg/kg/2 weeks). In 2018, the dosage regimen was changed to flat dose (FD) administration (240 mg/2 weeks or 480 mg/4 weeks) based on a modeling study, without clinical data.

Methods: AM patients have been prospectively included in the French national multicenter MelBase database since 2013. First-line patients treated with nivolumab monotherapy were included in the WAD or FD groups of this study. The primary end point was the incidence of grade ≥3 immune-related adverse events (irAEs). Secondary end points were incidence of any grade irAEs, and overall survival (OS) and progression-free survival (PFS). Inverse probability of treatment weighting was used to balance groups on their baseline characteristics.

Results: Between 2015 and 2022, 348 patients were included: 160 in the WAD and 188 in the FD groups. In the FD group, 45% and 27% of patients weighed <75 kg and >85 kg, respectively. Grade ≥3 and any grade irAEs rates were 13.1% versus 11.7% (p = .8) and 63.1% versus 67.0% (p = .5) in the WAD and FD groups, respectively. After weighting, median PFS was 3.1 and 3.7 months (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.65-1.07), and median OS was 24.8 and 37.0 months (HR, 0.74; 95% CI, 0.54-1.01) in the WAD and FD groups, respectively.

Conclusions: There was no difference in the incidence of severe irAEs and in median PFS between AM patients treated by WAD or FD nivolumab. The median OS between patient groups did not reach statistical significance.

Keywords: delivery of health care; dose–response relationship; drug; health services research; immune checkpoint inhibitors; melanoma.

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Conflict of interest statement

Laurent Mortier reports participating on expert boards for Bristol‐Myers Squibb, MSD, Pierre Fabre, Novartis, and Sanofi. Olivier Dereure reports honoraria from Bristol‐Myers Squibb, MSD, Novartis, Pierre Fabre, Leo Pharma, Recordati Rare Diseases, Kyowa Kirin, Amgen, Sanofi; participation in clinical trials with Bristol‐Myers Squibb, Kyowa Kirin, MSD, Novartis, Pierre Fabre, Regeneron; and travel grants from Bristol‐Myers Squibb, Pierre‐Fabre, Novartis, Recordati Rare Diseases, Kyowa Kirin, and Amgen. Sophie Dalac Rat reports participating on expert board for Bristol‐Myers Squibb, Pierre Fabre, and Novartis; participation in clinical trials with Bristol‐Myers Squibb, Pfizer, Amgen, GSK, Roche, Novartis, Pierre Fabre, Cerpass, MSD, Kartos, Huyabio, Regeneron; and travel grants from Bristol‐Myers Squibb, and Pierre‐Fabre. Henri Montaudié reports honoraria from Bristol‐Myers Squibb, Merck Serono, MSD, Novartis, Pierre Fabre; institutional support from Bristol‐Myers Squibb, Leo Pharma; participation in clinical trials with Bristol‐Myers Squibb, Checkpoint Therapeutics, Huya Bioscience, Incyte, Merck Serono, MSD, Nektar Pharmaceuticals, Novartis, Pierre Fabre, Regeneron, Replimmune; and travel grants from Bristol‐Myers Squibb, Pierre‐Fabre, and Novartis. Cecile Pagès reports participating on an expert board for Bristol‐Myers Squibb. Florence Brunet‐Possenti reports honoraria from Bristol‐Myers Squibb, MSD, Pierre Fabre, and Novartis. Celeste Lebbé reports honoraria from Roche, Bristol‐Myers Squibb, Novartis, Amgen, MSD, Pierre Fabre, Pfizer, and Incyte; consulting or advisory roles with Bristol‐Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Speakers' Bureau of Roche, Bristol‐Myers Squibb, Novartis, Amgen, and MSD; research funding from Roche and Bristol‐Myers Squibb; travel and accommodations expenses from Bristol‐Myers Squibb, MSD, Novartis, Sanofi, and Pierre Fabre; and Board participation with Avantis Medical Systems, InflaRx, Sanofi, BMS, MSD, Pierre Fabre, Novartis, and Jazz Pharmaceuticals. Caroline Gaudy‐Marqueste reports honoraria from Bristol‐Myers Squibb and Pierre Fabre; participation in clinical trials with BMS, Pfizer, Amgen, GSK, Roche, Novartis, Pierre Fabre, Cerpass, MSD, Janssen, Kartos, IFX, Huyabio, Astex, Regeneron, IO Biotech, Philogen, Sotio, Kinnate, and Astra Zenecca; and travel grants from Bristol‐Myers Squibb, Pierre‐Fabre, and MSD. Philippe Saiag reports honoraria from Roche, Bristol‐Myers Squibb, Novartis, MSD, Pierre Fabre, Pfizer, and Incyte; consulting or advisory roles for Bristol‐Myers Squibb, MSD, Novartis, Merck Serono, Sanofi, and Pierre Fabre; funding from Roche; and travel, accommodations, and expenses from Bristol‐Myers Squibb, MSD, Novartis, and Pierre Fabre. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier curves of AM patient overall survival in the WAD and in the FD nivolumab monotherapy groups, adjusted by inverse probability of treatment weighting. AM indicates advanced melanoma; CI, confidence interval; FD, flat dose; HR, hazard ratio; OS, overall survival; WAD, weight‐adjusted dose.
FIGURE 2
FIGURE 2
Kaplan–Meier curves of AM patients PFS in the WAD and in the FD nivolumab monotherapy groups, adjusted by inverse probability of treatment weighting. AM indicates advanced melanoma; CI, confidence interval; FD, flat dose; HR, hazard ratio; OS, overall survival; PFS, progression‐free survival; WAD, weight‐adjusted dose.
See this image and copyright information in PMC

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