A multicenter clinical study conducted across several Dutch and Belgian medical institutions and led by Prof. Cornelis Punt (former AMC) and Dr. Rutger-Jan Swijnenburg of Cancer Center Amsterdam compared the most active first-line treatment regimens for shrinking tumors initially deemed too large for surgery. The study results, known as CAIRO5, were published in Th Lancet Oncology.

First-line treatment regimens, also known as induction systemic treatment, refers to the initial, intensive phase of chemotherapy or other drug therapies given at the beginning of treatment for advanced cancer. The goal of induction therapy for patients with advanced liver metastases of colorectal cancer is to shrink large tumors to potentially make surgical treatment a viable option.

CAIRO5

The randomized, open-label, phase 3 study focused on colorectal cancer patients who presented with unresectable liver metastases. A total of 530 patients were divided into four groups (A, B, C, and D), each receiving different combinations of chemotherapy agents and targeted therapies.

Group A received chemotherapy regimens FOLFOX or FOLFIRI in combination with bevacizumab, a drug known to inhibit the formation of new blood vessels in tumors. Group B was additionally administered FOLFOXIRI in combination with bevacizumab, an intensive combination chemotherapy. For patients with specific genetic characteristics (left-sided and RAS and BRAFV600E wild-type tumors), groups C and D were given FOLFOX or FOLFIRI with either bevacizumab or panitumumab, another targeted therapy.

After a median follow-up of over four years, the research team found that patients in group B had a longer period without their cancer worsening (median progression-free survival of 10.6 months) compared to group A (9.0 months). However, the groups receiving panitumumab (C and D) did not show any significant clinical benefit over those receiving bevacizumab, and they experienced more adverse effects.

A delicate balance

Notably, the treatment regimens did lead to serious side effects, such as neutropenia, hypertension, and diarrhea. Group B, the most effective treatment group, also experienced the highest number of serious adverse events, leading to seven treatment-related deaths.

The study concluded that for patients with initially unresectable colorectal cancer liver metastases, FOLFOXIRI combined with bevacizumab is the preferred treatment for patients with a right-sided or RAS or BRAFV600E mutated primary tumor. In patients with a left-sided and RAS and BRAFV600E wild-type tumor, the study demonstrated that adding panitumumab to the treatment mix does not provide clinical benefits and may increase toxicity.

These findings offer valuable insights into more effective and personalized treatment plans for patients with advanced colorectal cancer.

For more information, contact Dr. Rutger-Jan Swijnenburg, or read the scientific publication: Marinde J G Bond, M.J.G., et al. (2023) First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group. The Lancet Oncology. https://doi.org/10.1016/S1470-2045(23)00219-X.

People involved at Amsterdam UMC

Karen Bolhuis (former AMC)

Cornelis Punt (former AMC)

Rutger-Jan Swijnenburg

Geert Kazemier

Marc R W Engelbrecht

Funding

Financial support for this clinical investigation was provided by Roche and Amgen.

Text by Laura Roy.

This article was created forCancer Center Amsterdam.

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