The efficacy and safety of first-line metastatic melanoma treatment with ipilimumab + nivolumab versus nivolumab in a real-world setting

Billard Karine; Laurent Mortier; Olivier Dereure; Sophie Dalac; Henri Montaudié; Delphine Legoupil; Caroline Dutriaux; Julie De Quatrebarbes; Eve Maubec; Marie-Thérèse Leccia; Florence Granel-Brocard; Florence Brunet-Possenti; Jean-Philippe Arnault; Caroline Gaudy-Marqueste; Cecile Pages; Philippe Saiag; Jean-Matthieu L'orphelin; Ouidad Zehou; Thierry Lesimple; Clara Allayous; Raphael Porcher; Bastien Oriano; Stephane Dalle; Céleste Lebbé

doi:10.1093/bjd/ljae470

The efficacy and safety of first-line metastatic melanoma treatment with ipilimumab + nivolumab versus nivolumab in a real-world setting

Br J Dermatol. 2024 Nov 28:ljae470. doi: 10.1093/bjd/ljae470. Online ahead of print.

Authors

Billard Karine¹, Laurent Mortier², Olivier Dereure³, Sophie Dalac⁴, Henri Montaudié⁵, Delphine Legoupil⁶, Caroline Dutriaux⁷, Julie De Quatrebarbes⁸, Eve Maubec⁹, Marie-Thérèse Leccia¹⁰, Florence Granel-Brocard¹¹, Florence Brunet-Possenti¹², Jean-Philippe Arnault¹³, Caroline Gaudy-Marqueste¹⁴, Cecile Pages¹⁵, Philippe Saiag¹⁶, Jean-Matthieu L'orphelin¹⁷, Ouidad Zehou¹⁸, Thierry Lesimple¹⁹, Clara Allayous¹, Raphael Porcher²⁰, Bastien Oriano¹, Stephane Dalle²¹, Céleste Lebbé¹

Affiliations

¹ Service d'onco-dermatologie, Hôpital Saint Louis APHP, 1 avenue Claude Vellefaux, 75010 Paris.
² Service de dermatologie, Hôpital Claude Huriez, Rue Michel Polonovski, 59037 Lille.
³ Service de dermatologie et INSERM U1058, Université de Montpellier, 34000 Montpellier.
⁴ Service de Dermatologie UMAC, Hôpital Dijon Bourgogne, 14 rue Paul Gaffarel, BP 77908, 21079 Dijon.
⁵ Service de dermatologie, Hôpital de l'Archet - CHU de Nice, 151 route de Saint-Antoine, 06200 Nice.
⁶ Service de dermatologie, Hôpital Morvan - CHRU De Brest, 2 avenue Foch, 29609 Brest.
⁷ Service d'onco-dermatologie, Hôpital Saint-André - CHU de Bordeaux, 1 rue Jean Burguet, 33000 Bordeaux.
⁸ Service de dermatologie, CH Annecy Genevois, 1 avenue de l'hôpital, 74370 Annecy/Metz Tessy.
⁹ Service de dermatologie, Hôpital Avicenne APHP, Université Sorbonne Paris Nord, 93022 Bobigny.
¹⁰ Service de dermatologie, CHU Grenoble - Albert Michallon, Avenue du Grésivaudan, 38700 La Tronche.
¹¹ Service de dermatologie, CHRU de Nancy - Hôpitaux de Brabois, 54500, Vandœuvre-lès-Nancy.
¹² Service de dermatologie, Hôpital Bichat Claude-Bernard AP-HP, Université Paris Cité, Paris.
¹³ Service de Dermatologie, CHU Amiens - Picardie, 1 Rue du Professeur Christian Cabrol, 80000 Amiens.
¹⁴ Service de dermatologie et de cancérologie cutanée, CHU Timone AP-HM, 264 Rue Saint-Pierre, 13005 Marseille.
¹⁵ Service de dermatologie, CHU Toulouse - Hôpital Larrey, 24 Chemin De Pouvourville, 31059 Toulouse.
¹⁶ Service de Dermatologie Générale et Oncologique, Hôpital Ambroise Paré AP-HP, Université Paris Saclay, 9 Avenue Charles De Gaulle 92104 Boulogne.
¹⁷ Service de Dermatologie, CHU de Caen, Avenue de la côte de Nacre, 14033 Caen.
¹⁸ Service de dermatologie, CHU Henri Mondor AP-HP, 94000 Créteil, France.
¹⁹ Service d'oncologie médicale, CRLCC Eugène Marquis, 5 Rue Bataille Flandres-dunkerque, 35000 Rennes.
²⁰ Service d'épidémiologie clinique, Hôpital Hotel-Dieu, ,1 place du Parvis Notre-Dame, 75004 Paris.
²¹ Service de dermatologie, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, 69000 Lyon.

PMID: 39605282
DOI: 10.1093/bjd/ljae470

Abstract

Background: The Checkmate 067 randomized controlled trial, published in 2015, demonstrated improved progression-free survival and numerically, although not statistically, superior overall survival for ipilimumab + nivolumab. The objective of this study was to compare the efficacy and safety of nivolumab to ipilimumab + nivolumab as first-line treatment for metastatic melanoma in a real-world setting.

Methods: Patients were prospectively included in the French Melbase cohort from 2013 to 2022. Eligible patients were those in first-line treatment for stage-IIIc or -IV melanoma, undergoing immunotherapy with nivolumab or ipilimumab + nivolumab. The primary endpoint was overall survival at 36 months. The secondary endpoints included progression-free survival at 36 months, best radiological response, and safety analyses. We conducted a propensity score using the IPTW method to overcome the various confounding factors and also a subgroup analysis (brain metastasis, LDH levels, and BRAF mutation status).

Results: A total of 406 patients were treated with nivolumab, and 416 with ipilimumab + nivolumab. Overall survival at 36 months was higher in the ipilimumab + nivolumab group (57.1%, ([95%CI 50.7-64.2]) than in the nivolumab group (46.6% [95%CI 41.6-52.1]), HR 1.4[1.1;1.8]. Progression-free survival at 36 months was significantly improved in the ipilimumab + nivolumab group (42.3%) compared to the nivolumab group (21.9%), with a HR 1.6[1.4;1.9]. The objective response rate was similar for the two groups (44%). The overall incidence of side effects was comparable (82 vs. 84%), and severe toxicity (grade ≥ 3) was more frequent, though not significantly so, in the ipilimumab + nivolumab arm (29% vs. 41%).

Conclusions: Our results are consistent with those from the Checkmate 067 study, except for the objective response rate and the incidence of toxicities, which proved to be lower in our analysis.

© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.