Insights into the future of first-line advanced hepatocellular carcinoma treatment

Mené sur 58 patients atteints d'un carcinome hépatocellulaire non résécable de stade localement avancé ou métastatique (âge médian : 65 ans ; 79 % d'hommes), cet essai "parapluie" de phase 1b/2 évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité de l'ajout du tiragolumab à un traitement combinant atézolizumab et bévacizumab

Résumé en anglais

Atezolizumab plus bevacizumab is the standard of care for patients with advanced hepatocellular carcinoma. Building on the impressive results of IMBrave150,1 the phase 1b–2 MORPHEUS-Liver trial2 compared another dual immune checkpoint inhibitor regimen, the combination of atezolizumab plus bevacizumab with the first-in-class anti-TIGIT antibody tiragolumab, with atezolizumab plus bevacizumab alone. Tiragolumab could improve on the efficacy of atezolizumab plus bevacizumab through its diverse effects on CD8+ T cells, regulatory T cells, and tumour-associated macrophages. TIGIT is an inhibitory molecule on CD8+ T cells with CD155 (poliovirus receptor [PVR]) as its ligand. Preclinical studies have shown that in hepatocellular carcinoma cells, CD111 (PVRL1) is upregulated and stabilises PVR, promoting interaction with TIGIT. In anti-PD-1-resistant hepatocellular carcinomas,3 TIGIT has high expression and maintains T-cell exhaustion, and combined anti-PD1 and anti-TIGIT blockade significantly reduced tumour growth.3 Additionally, in the CITYSCAPE trial, high baseline tumour-associated macrophages and regulatory T cells were associated with better overall survival in patients who received atezolizumab plus tiragolumab but not atezolizumab alone.4 In preclinical models, tiragolumab surrogate antibodies were found to remodel immunosuppressive tumour microenvironments, independent of TIGIT blockade, by engaging Fc