Combining the clinical biomarkers of primary tumor sidedness and liver-limited disease status may improve the selection of optimal patients for targeted first-line treatment for RAS wild-type metastatic colorectal cancer, according to results from a phase 3 trial.

These results were presented by Julian Holch, MD, LMU Munich and German Cancer Consortium, Munich, Germany, at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium on Saturday, January 20, 2024, in San Francisco, California.

According to Dr Holch and coauthors, selection for first-line treatment with EGFR agents among patients with metastatic colorectal cancer “is based on primary tumor sidedness with anti-EGFR being the preferred option for patients with left-sided [metastatic colorectal cancer]” while patients with right-sided metastatic colorectal cancer “are preferentially treated in combination with bevacizumab” to target VEGF.

In the FIRE-3 trial, 400 patients with RAS wild-type metastatic colorectal cancer received either FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab in the first-line setting. Using models, pairwise combinations of clinical biomarkers were evaluated. The biomarkers included were: primary tumor sidedness, age, sex, liver-limited disease status, and baseline carcinoembryonic antigen serum level. The model with the best test statistics and P-value was chosen for further evaluations.

The model that best predicted outcomes in either treatment arm was the combination of primary tumor sidedness and liver-limited disease status (P = .005). A survival benefit with FOLFIRI plus cetuximab over FOLFIRI plus bevacizumab was observed among patients with left-sided colorectal cancer and non–liver-limited disease when compared with those patients with left-sided colorectal cancer and liver-limited disease. Among patients with right-sided colorectal cancer and non–liver-limited disease, there was a significant improvement in overall survival with FOLFIRI plus bevacizumab vs FOLFIRI plus cetuximab. However, patients with right-sided colorectal cancer and liver-limited disease had a benefit with FOLFIRI plus cetuximab rather than FOLFIRI plus bevacizumab.

Source:

Holch JW, Ohnmacht A, Stintzing S, 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). Presented at 2024 ASCO Gastrointestinal Cancer Symposium; January 18-20, 2024; San Francisco, California. Abstract 13