Impact of the tumor immune contexture in microsatellite-stable metastatic colorectal cancer treated with avelumab, cetuximab, and irinotecan
(2025) Cell Reports Medicine — Vol. 6, n° 7, p. 102201 (2025)
Files
Impactofthetumorimmunecontextureinmicrosatellite-stablemetastaticcolorectalcancertreatedwithavelumabcetuximaband.pdf
Open Access - Adobe PDF
- 11.06 MB
Details
- Authors
- Abstract
- The treatment of patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) remains a significant clinical challenge. Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal anti body (mAb), induces immunogenic cell death, potentially synergizing with immune checkpoint inhibitors. The phase 2, proof-of-concept, single-arm AVETUXIRI trial (ClinicalTrials.gov: NCT03608046) evaluates the safety and efficacy of cetuximab, irinotecan (a topoisomerase I inhibitor), and avelumab (an anti-programmed cell death ligand 1 [PD-L1]) in 57 patients with RAS wild-type or mutated MSS mCRC refractory to chemo therapy and anti-EGFR mAbs. Exploratory objectives include investigating the tumor immune microenviron ment within mCRC biopsies performed during the trial and correlating it with treatment activity. A manage able safety profile is observed. Although the overall efficacy endpoints are not met, biomarkers associated with clinical efficacy are identified. Patients exhibiting a high Immunoscore, strong cytotoxic and T cell prox imity to tumor cells, and a high genetic immunoediting score within mCRC biopsies before treatment demon strate significant therapeutic survival benefit, independent of RAS tumor mutation status
- Affiliations
Citations
Huyghe, N., Benidovskaya, E., Masoodi, T., Sinapi, I., De Cuyper, A., Vempalli, F., Beyaert, S., Bouzin, C., Osorio, F. M., Ferraro, L., van Baren, N., Helaers, R., Goffette, P., Ghaye, B., Van Maanen, A., Castella, M.-L., Ceccarelli, M., Bedognetti, D., Galon, J., et al. (2025). Impact of the tumor immune contexture in microsatellite-stable metastatic colorectal cancer treated with avelumab, cetuximab, and irinotecan. Cell Reports Medicine, 6(7), 102201. https://doi.org/10.1016/j.xcrm.2025.102201 (Original work published 2025)