AtezoTRIBE: a randomised phase II study of FOLFOXIRI plus bevacizumab alone or in combination with atezolizumab as initial therapy for patients with unresectable metastatic colorectal cancer

BMC Cancer
Carlotta AntoniottiChiara Cremolini

Abstract

Immune checkpoint inhibitors (ICIs) reported remarkable achievements in several solid tumours. However, in metastatic colorectal cancer (mCRC) promising results are limited to patients with deficient mismatch repair/microsatellite instability-high (dMMR/MSI-high) tumours due to their immune-enriched microenvironment. Combining cytotoxic agents and bevacizumab in mCRC with proficient mismatch repair/microsatellite stability (pMMR/MSS) could make ICIs efficacious by increasing the exposure of neoantigens, especially with highly active chemotherapy regimens, inducing immunogenic cell death, increasing the tumoral infiltration of CD8+ T-cells and reducing tumour-associated myeloid-derived suppressor cells. VEGF-blockade also plays an immunomodulatory role by inhibiting the expansion of T regulatory lymphocytes. Consistently with this rationale, a phase Ib study combined the anti-PDL-1 atezolizumab with FOLFOX/bevacizumab as first-line treatment of mCRC, irrespective of microsatellite status, and reported interesting activity and efficacy results, without safety concerns. Phase III trials led to identify FOLFOXIRI plus bevacizumab as an upfront therapeutic option in selected mCRC patients. Drawing from these considerations, the comb...Continue Reading

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Citations

Nov 19, 2020·Journal of Experimental Pharmacology·Sarah K Cimino, Cathy Eng
Feb 5, 2021·Journal of the Anus, Rectum and Colon·Akira OokiKensei Yamaguchi
Feb 18, 2021·Journal of Surgical Oncology·Melissa A Lumish, Andrea Cercek
Apr 4, 2021·Cancers·Torben Frøstrup HansenPer Pfeiffer
Apr 10, 2021·Cellular Oncology (Dordrecht)·Jamal Majidpoor, Keywan Mortezaee
Jul 25, 2021·Cancers·Norman J GalbraithColin W Steele

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Clinical Trials Mentioned

NCT03721653

Software Mentioned

AtezoTRIBE
MODUL

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