Clinical biomarkers may guide therapy selection in RAS wildtype mCRC

Presented by

Dr Julian Holch, Ludwig-Maximilians-University of Munich, Germany

Conference

ASCO GI 2024

Trial

Phase 3, FIRE-3 (AIO KRK0306)

Doi
https://doi.org/10.55788/e844b978

Combining certain clinical biomarkers may improve patient selection for targeted first-line therapy in patients with RAS wildtype metastatic colorectal cancer (mCRC), a substudy of the phase 3 FIRE-3 trial showed. Primary tumour side and liver-limited disease status were identified as relevant for this purpose.

Dr Julian Holch (Ludwig-Maximilians-University of Munich, Germany) and co-investigators performed a study that evaluated the predictive value of various clinical biomarkers on overall survival (OS) in the 2 treatment arms of the phase 3 FIRE-3/AIO KRK0306 trial (NCT00433927). In this study, patients with RAS wildtype mCRC were allocated to FOLFIRI plus cetuximab or to FOLFIRI plus bevacizumab. The primary analysis demonstrated that participants receiving cetuximab outperformed those receiving bevacizumab with regard to OS [1].

The combination of primary tumour side and liver-limited disease (LLD) status had the highest predictive value of therapy selection on OS [2]. In patients with left-sided tumours and no LLD (n=201), FOLFIRI plus cetuximab was the most effective therapy option (HR 0.62; P=0.02). In contrast, there was no significant difference between the effect of the 2 therapies on OS in the population of participants with left-sided tumours and LLD (n=106; HR 0.83; P=0.40). In patients with right-sided tumours and no LLD (n=61), FOLFIRI plus bevacizumab was the favoured therapy (HR 2.09; P=0.01), whereas FOLFIRI plus cetuximab had a numerical, but non-significant advantage over FOLFIRI plus bevacizumab in patients with right-sided tumours and LLD (n=27; HR 0.59; P=0.22).

“These findings indicate that interactions and combinations of biomarkers should be considered to increase their predictive accuracy regarding the treatment of mCRC,” argued Dr Holch.

Heinemann V, et al. Br J Cancer. 2021;124(3):587-594.
Holch JW, et al. Refining first-line treatment decision in RAS wildtype (RAS-WT) metastatic colorectal cancer (mCRC) by combining clinical biomarkers: results of the randomized phase 3 trial FIRE-3 (AIO KRK0306). Abstract 13, ASCO Gastrointestinal Cancers Symposium 2024, 18–20 January, San Francisco, CA, USA.

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