Evaluation of the flipped dose NIVO3+IPI1 in patients with advanced unresectable melanoma
Menée dans un contexte de vie réelle à partir de données portant sur 399 patients atteints d'un mélanome non résécable (hors mélanome de l'uvée) inclus dans deux essais, cette étude compare l'efficacité, du point de vue du taux de réponse objective, de la survie sans progression et de la survie globale, de deux stratégies thérapeutiques combinant nivolumab et ipilimumab (nivolumab 1 mg/kg et ipilimumab 3 mg/kg ou nivolumab 3 mg/kg et ipilimumab 1 mg/kg)
Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) was approved for advanced melanoma in 2016. The CheckMate 511 trial demonstrated improved tolerability with the flipped dose, NIVO3+IPI1, but this regimen has not been approved in melanoma by regulatory authorities. In this study, patients with advanced unresectable melanoma treated with NIVO3+IPI1 or NIVO1+IPI3 were included. The objective response rate was 48.8% with NIVO3+IPI1 (n = 209) and 36.9% with NIVO1+IPI3 (n = 190) (P = .016). Adjusted hazard ratio (aHR) was 0.67 (95% CI = 0.53 to 0.87, P = .002) for progression-free survival and 0.59 (95% CI = 0.44 to 0.78, P < .001) for overall survival (OS). In most studied subgroups aHR was <1, in favor of NIVO3+IPI1. The incidence of grade 3-5 immune-related adverse events was 30.6% with NIVO3+IPI1 vs. 51.1% with NIVO1+IPI3 (P < .001). This study shows that in a real-world setting, NIVO3+IPI1 demonstrated superior efficacy compared with NIVO1+IPI3, possibly related to a beneficial safety and tolerability profile allowing for more received doses.
Journal of the National Cancer Institute , résumé, 2025