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Can HER2 Status Predict Response to EGFR-Targeted Therapies in Colorectal Cancer?

By: Joseph Fanelli
Posted: Friday, May 3, 2019

Findings presented in The Oncologist indicate that patients with metastatic colorectal cancer who are HER2 positive seem to be less likely to respond to anti-EGFR therapy. Because of the predictive capability of this biomarker, testing for HER2 should be offered to all patients with metastatic colorectal cancer, concluded Salvatore Siena, MD, of the Università degli Studi di Milano, Milan, Italy, and colleagues.

“The present study confirmed that this molecular feature was associated with worse objective tumor response and shorter progression‐free survival in response to previous anti‐EGFR therapies,” the authors observed. “HER2 status assessment should be included in the molecular diagnostic workup of all [metastatic colorectal cancers] for speedy referral to clinical trials encompassing HER2‐targeted double blockade independently of previous anti‐EGFR treatment.”

Molecular screening for HER2 positivity was conducted in patients with KRAS exon 2 wild-type metastatic colorectal cancer. A sample of consecutive HER2-negative patients was selected as a control, and a regression modeling strategy was applied to identify predictors explaining HER2 positivity and its association with response to previous anti-EGFR treatment.

Of 1,485 KRAS exon 2 wild-type–screened patients, 100 HER2-positive metastatic colorectal cancer tumors were detected (6.7%). Those HER2-positive patients demonstrated a higher frequency of lung metastases (odds ratio = 2.04) and a higher tumor burden (odds ratio = 1.48). Tumors were also likely to be left-sided (odds ratio = 0.50), and patients who received treatment with anti-EGFR agents (79 individuals) displayed poor outcomes in terms of objective response rate (31.2%) and progression-free survival (5.7 months). Patients with HER2-negative status had a better objective response rates (46.9%) and progression-free survival (7 months).

Disclosure: The study authors’ disclosure information may be found at theoncologist.alphamedpress.org.



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