Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Treatment and RAS Mutations in Colorectal Cancer

Abstract

In the first-line treatment of mCRC, patients with RAS wild-type tumors derived a significant benefit from the addition of cetuximab to FOLFIRI; patients with RAS tumor mutations did not. Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy, thereby allowing the further tailoring of cetuximab administration to maximize patient benefit.

S3-Leitlinie – Kolorektales Karzinom

“…Auch diese Evaluation zeigte, dass Cetuximab bei RAS-mutierten Tumoren nicht wirksam war, allerdings wurde hier kein negativer Einfluss auf Effektivitäsparameter beobachtet [1042].…”

“…Quellen: [1109] Konsens Hintergrund Anti-EGFR-Antikörper zeigen keine Effektivität bei Vorliegen einer RAS-Mutation und sollen daher nicht eingesetzt werden [1041,1042,1045]. Prospektive Untersuchungen, welche die Effektivität von anti-VEGF-Substanzen in der Erstlinientherapie von Tumoren mit RAS-Mutation untersuchen, liegen nicht vor.…”

Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis

“…RAS mutations, including both KRAS and NRAS gene mutations, have been reported in about 50% of primary CRC, and have been associated with resistance to the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs), Cetuximab and Panitumumab, in the metastatic disease (Rizzo et al, 2010;Bronte et al, 2011). This has been well exploited by several randomized trials (De Roock et al, 2010;Bokemeyer et al, 2012;Douillard et al, 2013;Heinemann et al, 2014;Schwartzberg et al, 2014;Van Cutsem et al, 2015;Bokemeyer et al, 2015), that have overall shown significant poorer response rates and inferior survival outcomes in RAS-mutated patients receiving chemotherapy plus anti-EGFR MoAbs, compared to RAS-wild type population. RAS mutations represent the only, molecular, predictive biomarker approved for clinical use, while their prognostic role is still debated.…”

Nanofluidic Digital PCR and Extended Genotyping of RAS and BRAF for Improved Selection of Metastatic Colorectal Cancer Patients for Anti-EGFR Therapies

“…However, recent studies have demonstrated that other RAS mutations (exons 3 and 4 of KRAS and exons 2,3 and 4 of NRAS) are predictive of resistance to anti-EGFR drugs (3,4). These findings led most of the regulatory agencies and the major clinical guidelines to restrict the use of cetuximab and panitumumab to patients with wild-type RAS (including KRAS exons 2/3/4 and NRAS exons 2/3/4) tumors.…”