Metastatic Colorectal Cancer (RAS-wildtype) After Response to First-line Treatment With FOLFIR Plus Cetuximab

Summary

The FIRE-4 study aims to define a treatment concept for patients with RAS wild-type tumours, optimised with regard to overall survival. The first-line treatment will be conducted with FOLFIRI plus cetuximab, which resulted in a significantly prolonged overall survival versus bevacizumab in the FIRE-3 study. Following initial progression (PD1) it is recommended that the treatment be continued with FOLFOX plus bevacizumab, as this concept led to significantly prolonged survival in the E3200 study. Owing to the encouraging results of the Santini study , a cetuximab rechallenge in combination with irinotecan-based chemotherapy is to be performed as part of the third-line treatment in patients who showed a response defined according to RECIST 1.1 during the first-line treatment (tumour diameter \< -30%) or presented with stable tumour disease for at least 6 months (tumour diameter +20 to -30%). The concept of the ideal sequence has not yet been studied to date in a clinical trial.

Timeline

Start

2015-03

Primary completion

2025-01-30

Completion

2025-01-30

Publications

• Stintzing S, Klein-Scory S, Fischer von Weikersthal L, Fuchs M, Kaiser F, Heinrich K, Modest DP, Hofheinz RD, Decker T, Gerger A, Angermeier S, Rumpold H, Dickhut A, Ohler L, Gruenberger B, Niedersuess-Beke D, Sandmann M, Winder T, Trojan J, Prager G, Held S, Kumbrink J, Schmiegel W, Baraniskin A, Heinemann V. Baseline Liquid Biopsy in Relation to Tissue-Based Parameters in Metastatic Colorectal Cancer: Results From the Randomized FIRE-4 (AIO-KRK-0114) Study. J Clin Oncol. 2025 Apr 20;43(12):1463-1473. doi: 10.1200/JCO.24.01174. Epub 2025 Feb 4.

Drugs

Indications