Les conjugués anticorps‑médicament dans le cancer du sein : paysage actuel et cibles futures
Résumé
Les conjugués anticorps-médicaments (CAM) ont transformé les options thérapeutiques pour les patientes atteintes d’un cancer du sein, en permettant d’administrer des agents cytotoxiques ciblés plus efficaces, bien qu’accompagnés d’une toxicité systémique. Depuis l’autorisation du trastuzumab emtansine en 2012, le paysage des CAM s’est rapidement élargi pour inclure des agents ciblant HER2, TROP-2 et d’autres cibles nouvelles. Actuellement, quatre CAM sont approuvés dans le cancer du sein, montrant un bénéfice clinique dans les sous-types HER2-positif, HER2-faible, récepteurs hormonaux positifs et triple négatif. Le trastuzumab déruxtécan a démontré des résultats supérieurs à ceux des CAM précédents ciblant HER2; il constitue le traitement de choix dans plusieurs contextes. Les CAM anti-TROP-2, comme le sacituzumab govitecan et le datopotamab déruxtécan, ont amélioré la survie sans progression chez les patientes atteintes d’un cancer triple négatif et dans la maladie à RH-positif/HER2-négatif. Les recherches en cours explorent d’autres cibles, telles que HER3, Nectin-4, B7-H4 et CD166, et plusieurs médicaments candidats prometteurs ont démontré leur efficacité lors d’essais cliniques précoces. À mesure que les CAM sont utilisés dans des lignes de traitement plus précoces et dans des schémas thérapeutiques d’association, il sera essentiel de comprendre la séquence optimale des agents, la gestion de la toxicité et les considérations financières. Cette revue fera le point sur la place actuelle des CAM dans le traitement du cancer du sein et mettra en évidence les orientations futures de cette classe thérapeutique en pleine évolution.
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