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Posted by on Jan 8, 2023 in Colorectal cancer | 0 comments

In a nutshell

This study evaluated the effectiveness and safety of FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab (Avastin) with or without atezolizumab (Tecentriq) on the outcomes of patients with metastatic (m) colorectal cancer (CRC). The study showed that adding atezolizumab to FOLFOXIRI plus bevacizumab regimen was safe and improved survival outcomes in these patients.

Some background

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. The early symptoms of CRC are often not reported. Patients are mostly diagnosed with CRC when their tumor has spread to distant organs (mCRC). The standard treatment for CRC is targeted therapy with chemotherapy. Targeted therapy such as bevacizumab targets a protein on cancer cells that blocks the formation of new blood vessels. This stops the tumor from growing and spreading.

Immunotherapy has also been successfully used to treat CRC. Immunotherapy uses the body's own immune system to fight cancer. Tumor cells try to avoid death by switching off our immune system. They bind to proteins on the immune cell surface such as PD-1/PD-L1 or CTLA-4. Immune checkpoint inhibitors (ICI) such as atezolizumab block those interactions and turn on the immune system to attack and kill cancer cells.

Most mCRCs have genetic mutations (abnormalities) that make them resistant to standard immunotherapy. These cancers are reported to have a proficient mismatch repair (pMMR) system and are microsatellite stable (MSS). It is important to evaluate whether adding atezolizumab to standard FOLFOXIRI chemotherapy and bevacizumab improves the outcomes of patients with pMMR and MSS mCRC.

Methods & findings

The study involved 218 patients with mCRC. 73 patients were randomly assigned to receive FOLFOXIRI chemotherapy plus bevacizumab (group 1). 145 patients receive FOLFOXIRI plus bevacizumab and atezolizumab (group 2). The average follow-up period was 19.9 months.

The average survival without cancer worsening was higher in group 2 (13.1 months) compared to group 1 (11.5 months). Patients in group 2 had a 31% higher chance of a better survival without cancer worsening compared to group 1.

Serious side effects occurred in 26% of patients in group 1 and 27% of patients in group 2. The most common side effects included low white cell counts with or without fever, and diarrhea. 

The bottom line

The study concluded that FOLFOXIRI plus bevacizumab with atezolizumab improved the survival without cancer worsening in patients with mCRC and was safe.

The fine print

The study was supported by Roche, the manufacturer of atezolizumab. The follow-up period and the number of participants were small. Larger studies are needed to further validate these findings.

Published By :

The Lancet. Oncology

Date :

May 27, 2022

Original Title :

Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial.

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