Regorafenib in combination with immune checkpoint inhibitors for mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer.

Autor: Akin Telli T; Department of Gastrointestinal Oncology, Institut Jules Bordet, Brussels, Belgium., Bregni G; Department of Gastrointestinal Oncology, Institut Jules Bordet, Brussels, Belgium; Université Libre de Bruxelles (ULB), Brussels, Belgium., Vanhooren M; Department of Gastrointestinal Oncology, Institut Jules Bordet, Brussels, Belgium., Saude Conde R; Department of Gastrointestinal Oncology, Institut Jules Bordet, Brussels, Belgium., Hendlisz A; Department of Gastrointestinal Oncology, Institut Jules Bordet, Brussels, Belgium; Université Libre de Bruxelles (ULB), Brussels, Belgium., Sclafani F; Department of Gastrointestinal Oncology, Institut Jules Bordet, Brussels, Belgium; Université Libre de Bruxelles (ULB), Brussels, Belgium. Electronic address: francesco.sclafani@bordet.be.
Jazyk: angličtina
Zdroj: Cancer treatment reviews [Cancer Treat Rev] 2022 Nov; Vol. 110, pp. 102460. Date of Electronic Publication: 2022 Aug 27.
DOI: 10.1016/j.ctrv.2022.102460
Abstrakt: 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 inflammatory tumour microenvironment with abundant tumour-infiltrating lymphocytes. Over the last few 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. Among these, the combination of ICIs with multi-kinase inhibitors has gained traction in preclinical studies and clinical trials. Thanks to their multiple targets and mechanisms of 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 efficiently recognised and targeted by an activated immune system. Regorafenib is routinely used for chemorefractory CRC with limited efficacy. Preliminary evidence, however, suggests that this multi-kinase inhibitor could be an optimal combination partner for ICIs. In this review article, we explain the biological rationale underlying the synergism between regorafenib and ICIs, discuss the available clinical data in CRC, and take a glance into future perspectives by presenting ongoing trials and possible research developments in this setting.
Competing Interests: Declaration of Competing Interest Alain Hendlisz - Consultancy, advisory roles, honoraria: Amgen, Bayer, Eli Lilly, Merck, Pierre Fabre, Servier, Sirtex. Research funding (inst): Amgen, Astra Zeneca, Ipsen, Leo Pharma, Merck, Roche, Sanofi, Teva Pharma. Travel grants: Merck, Roche, Sirtex. Francesco Sclafani - Consultancy, advisory roles, honoraria: AMAL Therapeutics, Bayer, BMS, Dragonfly Therapeutics, Nordic Pharma, Roche. Research funding (inst): Amgen, Astra Zeneca, Bayer, BMS, Roche, Sanofi. Travel grants: Amgen, Bayer, Lilly, Servier. Leadership roles: Co-Chair EORTC Task Force Colon, Rectum, Anal Canal. Other: Chief Investigator of the REGINA trial (NCT04503694). The other authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: