Phase II study on first-line treatment of NIV olumab in combination with folfoxiri/bevacizumab in patients with Advanced
- PDF / 549,701 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 2 Downloads / 222 Views
STUDY PROTOCOL
Open Access
Phase II study on first-line treatment of NIVolumab in combination with folfoxiri/ bevacizumab in patients with Advanced COloRectal cancer RAS or BRAF mutated – NIVACOR trial (GOIRC-03-2018) Angela Damato1,2* , Francesco Iachetta1, Lorenzo Antonuzzo3, Guglielmo Nasti4, Francesca Bergamo5, Roberto Bordonaro6, Evaristo Maiello7, Alberto Zaniboni8, Giuseppe Tonini9, Alessandra Romagnani1, Annalisa Berselli1, Nicola Normanno10 and Carmine Pinto1
Abstract Background: FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab has shown to be one of the therapeutic regimens in first line with the highest activity in patients (pts.) with metastatic colorectal cancer (mCRC) unselected for biomolecular alterations. Generally, tumors co-opt the programmed death-1/ligand 1 (PD-1/PDL1) signaling pathway as one key mechanism to evade immune surveillance. As today, anti-PD-1 monoclonal antibodies are FDA approved only for DNA mismatch repair deficient/microsatellite instability-high (MMRd/MSI-H), which represent only about 5% among all mCRC. Nowadays, there are no data demonstrating anti PD-1 activity in proficient and stable disease (MMRp/MSS). A different target in mCRC is also the Vascular Endothelial Growth Factor A (VEGF-A), which acts on endothelial cells to stimulate angiogenesis. VEGF-A inhibition with bevacizumab has shown to increase the immune cell infiltration, providing a solid rationale for combining VEGF targeted agents with immune checkpoint inhibitors. Based on these evidences, we explore the combination of triplet chemotherapy (FOLFOXIRI) with bevacizumab and nivolumab in pts. with mCRC RAS/BRAF mutant regardless of microsatellite status. (Continued on next page)
* Correspondence: [email protected] 1 Medical Oncology Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Oncologia Medica, Dipartimento Oncologico e Tecnologie Avanzate, Viale Risorgimento 80, 42123 Reggio Emilia, Italy 2 Department of Medical Biotechnologies, University of Siena, Strada delle Scotte 4, 53100 Siena, Italy Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Doma
Data Loading...
