FOLFOXIRI/Bevacizumab Plus Nivolumab as First-Line Treatment in Metastatic Colorectal Cancer RAS/BRAF Mutated: Safety Run-In of Phase II NIVACOR Trial

Abstract

The NIVACOR trial is a phase II study assessing the efficacy and safety of nivolumab in combination with FOLFOXIRI/bevacizumab in first-line setting in patients affected by metastatic colorectal cancer (mCRC) RAS/BRAF mutated. We report safety run-in results in the first 10 patients enrolled. Patients received triplet chemotherapy with FOLFOXIRI scheme plus bevacizumab, in association with nivolumab every 2 weeks for 8 cycles (induction phase) followed by bevacizumab plus nivolumab every 2 weeks (maintenance phase), until progression of disease or unacceptable toxicities. The first ten patients were evaluated: 7 experienced at least one adverse event (AE) related to FOLFOXIRI/bevacizumab and 2 related to nivolumab. The most frequent grade 1–2 AEs related to FOLFOXIRI/bevacizumab were diarrhea and fatigue (71%), nausea and vomiting (57%); 3 (43%) had grade 3–4 neutropenia, and 2 (20%) patients developed grade 1–2 AEs nivolumab related: skin rash and salivary gland infection. Two patients delayed the dose because of serious AEs, proteinuria and salivary gland infection; one patient discontinued experimental treatment due to the ileo-urethral fistula and concurrent Clostridium infection diarrhea. No treatment- related death occurred. The safety run-in analysis of NIVACOR trial reassured using co-administration of FOLFOXIRI/bevacizumab and nivolumab was well tolerated with an acceptable toxicity profile.Clinical Trial Registrationhttps://clinicaltrials.gov/, (NCT04072198).

JAML overexpression in tumour vascular endothelial cells promotes cancer proliferation via angiogenesis through VEGF signalling pathway activation

“…Downregulation of JAML in endothelial cells increases the number of pericytes around endothelial cells and improves tumour blood vessel permeability. Pericytes share a basement membrane with vessel endothelial cells, and their reciprocal interactions are crucial for endothelial cell barrier function [27].…”

Short bevacizumab infusion as an effective and safe treatment for colorectal cancer

“…Recently, bevacizumab has shown promise as an adjunct therapy that enhances the effects of immune checkpoint inhibitors in the management of non-small cell lung cancer (IMpower150 study) and renal cell cancer (IMmotion150 study) (19,20). In the field of colorectal cancer, phase II and III studies of bevacizumab plus immune checkpoint inhibitors plus cytotoxic chemotherapy have reported promising results (21)(22)(23). In future, the use of chemotherapy with bevacizumab is expected to increase, resulting in more infusions, and making short bevacizumab infusions increasingly important to reduce the infusion rate waiting times and increase patient convenience.…”

Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulation

“…Colorectal cancer (CRC) is the most common digestive tract tumor, accounting for approximately 9.7% of all cancer patients and approximately 8.5% of tumor-related deaths [ 1 ]. The standard treatment for metastatic CRC is chemotherapy combined with targeted therapy, such as anti-angiogenic agents (ramucirumab, bevacizumab or aflibercept) or anti-EGFR drugs (cetuximab or panitumumab) for patients with RAS wild-type [ 2 , 3 ]. However, in cases where these common treatments fail, treatment options are limited.…”