Liver Status Improves Targeted Therapy Selection in Mets CRC

TOPLINE:

Adding liver metastases status to primary tumor sidedness better predicts targeted therapy outcomes in RAS -wild-type metastatic colorectal cancer (CRC).

METHODOLOGY:

• In general, epidermal growth factor receptor blockers such as cetuximab are used alongside chemotherapy in patients with RAS-wild-type metastatic CRC who have left-sided primary tumors, while vascular endothelial growth factor inhibitors like bevacizumab are typically used for patients with right-sided primary tumors.
• To determine if combining biomarkers helps refine treatment selection and better predict patient outcomes, investigators ran an exploratory analysis of 400 participants enrolled in the FIRE-3 trial. The exploratory analysis pitted cetuximab against bevacizumab on a background of FOLFIRI chemotherapy in patients with RAS-wild-type metastatic CRC.
• The researchers assessed whether age, sex, baseline carcinoembryonic antigen level, primary tumor sidedness, and liver-limited disease status — whether metastases were confined to the liver — helped predict overall survival.

TAKEAWAY:

• When predicting overall survival outcomes, a model combining primary tumor sidedness and liver-limited disease status outperformed a model using primary tumor sidedness alone among patients in either treatment arm (C-index, 0.603; P = .005).
• In patients with left-sided primary tumors, cetuximab was associated with significantly improved overall survival compared with bevacizumab in patients with extrahepatic metastases (hazard ratio [HR], 0.62; P = .02). Cetuximab only demonstrated a trend toward a benefit in patients who had metastases confined to the liver (HR, 0.83; P = .40).
• In patients with right-sided primary tumors, bevacizumab beat out cetuximab in patients with extrahepatic metastases (HR, 2.09), while patients with metastases limited to the liver appeared to benefit more, but not significantly so, from cetuximab (HR, 0.59; P = .218).
• The findings held in patients with metastases confined to the liver even if they went on to later liver resection or ablation, suggesting that the outcomes probably reflect tumor biology.

IN PRACTICE:

Combining primary tumor sidedness and liver-limited disease status “might improve optimal patient selection for targeted first-line treatment” in RAS-wild-type metastatic CRC, but “validation in further datasets is warranted,” the authors concluded.

SOURCE:

The work, led by Julian Walter Holch of the Ludwig Maximilian University of Munich, Munich, Germany, was presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

LIMITATIONS:

The study was a retrospective review with relatively small numbers of patients in the various subgroups.

DISCLOSURES:

The work was funded by Merck. The lead investigator had no disclosures.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected].