Marker Could ID Lung Cancer Patients Likely to Benefit From EGFR Inhibition


Patients with stage IV squamous cell lung cancer positive for an EGFR gene copy number biomarker saw a survival benefit when adding cetuximab to chemotherapy.

Patients with stage IV squamous cell lung cancer positive for an EGFR-gene copy number biomarker, saw an overall survival (OS) benefit from the addition of the EGFR inhibitor cetuximab to chemotherapy, according to a secondary analysis from the large phase III SWOG SO819 study, presented at the 2015 World Conference on Lung Cancer in Denver, Colorado (late-breaking abstract 04.01).

No such survival benefit was seen among patients with non-squamous histology or cancers negative for the EGFR gene copy number biomarker, however. The larger SWOG SO819 study failed to show an OS benefit associated with cetuximab for the entire study population.

The study authors’ prior research had suggested that EGFR gene copy number, measured by fluorescent in-situ hybridization (FISH), could identify patients likely to benefit from adding cetuximab to chemotherapy.

“The addition of cetuximab had minimal effect on unselected advanced non–small-cell lung cancer (NSCLC) patients, but in FISH-positive patients there is a suggestion of benefit, predominantly in squamous cell lung cancer and bevacizumab-inappropriate patients,” reported lead study author Roy S. Herbst, MD, PhD, of the Yale Comprehensive Cancer Center in New Haven, Connecticut.

There was a “promising” but non-statistically significant trend toward longer median OS among EGFR FISH-positive patients who were administered cetuximab (n = 400; hazard ratio [HR], 0.83 [95% CI, 0.67–10.04]; P = .10).

In an analysis of bevacizumab-inappropriate EGFR FISH-positive patients, OS was significantly longer among patients who received cetuximab (n = 234; HR, 0.75 [95% CI, 0.57–0.998]; P = .048).

In a subsequent exploratory analysis, an OS benefit was also found in patients with squamous cell FISH-positive lung cancer (n = 101; HR, 0.56 [95% CI, 0.37–0.84]; P = .006), Herbst reported.

Cetuximab is a chimeric monoclonal antibody that targets epidermal growth factor receptor (EGFR). Previous studies had shown that cetuximab moderately increased patient survival in advanced NSCLC, Herbst noted.

“Squamous cell carcinoma is a minority subtype of lung cancer for which we have seen few new targeted therapies in the last 20 years,” Herbst noted. “These data are hypothesis generating, suggesting that EGFR FISH is a potential biomarker that can be used for study of cetuximab or similar drugs in the future.”

“These data support using the biomarker for determining who should receive an EGFR antibody inhibitor with chemotherapy, within the squamous subgroup,” he said.

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