Regorafenib in combination with immune checkpoint inhibitors for mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer
Cette étude passe en revue les données évaluant l'efficacité du régorafénib en combinaison avec des inhibiteurs de point de contrôle immunitaire chez des patients atteints d'un cancer colorectal avec microsatellites stables et ne présentant pas de déficience MMR
Résumé en anglais
Immune checkpoint inhibitors (ICIs) have marked a new era of cancer treatment, showing remarkable efficacy in a wide range of solid malignancies. In colorectal cancer (CRC),however, the therapeutic potential of ICIs is limited to the small group (≈5%) of patients with mismatch repair deficient (dMMR)/high microsatellite instable (MSI-H)tumours, which are characterised by high mutational/neo-antigen burden, and an inflammatorytumour microenvironment with abundant tumour-infiltrating lymphocytes. Over the lastfew years, research has focused on immuno-modulatory strategies that could overcome the inherent resistance to ICIs that is observed in the vast group (≈95%) of patients with mismatch repair proficient (pMMR)/microsatellite stable (MSS) tumours. Amongthese, the combination of ICIs with multi-kinase inhibitors has gained traction inpreclinical studies and clinical trials. Thanks to their multiple targets and mechanismsof action, generally involving key cancer pathways such as oncogenesis, angiogenesis,metastasis, and tumour immunity, these agents can exert synergistic effects with ICIs,eventually turning inherently cold cancers into hot tumours, that can be efficientlyrecognised and targeted by an activated immune system. Regorafenib is routinely used for chemorefractory CRC with limited efficacy. Preliminary evidence, however, suggeststhat this this multi-kinase inhibitor could be an optimal combination partner forICIs. In this review article, we explain the biological rationale underlying the synergismbetween regorafenib and ICIs, discuss the available clinical data in CRC, and takea glance into future perspectives by presenting ongoing trials and possible researchdevelopments in this setting.
