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Clinical Trial
. 2008 Jul 10;26(20):3351-7.
doi: 10.1200/JCO.2007.14.0111.

Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy

Fred R Hirsch  1 , Roy S Herbst, Christine Olsen, Kari Chansky, John Crowley, Karen Kelly, Wilbur A Franklin, Paul A Bunn Jr, Marileila Varella-Garcia, David R Gandara
Affiliations
Clinical Trial

Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy

Fred R Hirsch et al. J Clin Oncol. .

Abstract

Purpose: Epidermal growth factor receptor (EGFR) gene copy number detected by fluorescent in situ hybridization (FISH) has proven to be useful for selection of non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors. Here, we evaluate EGFR FISH as a predictive marker in NSCLC patients receiving the EGFR monoclonal antibody inhibitor cetuximab plus chemotherapy.

Patients and methods: Two hundred twenty-nine chemotherapy-naive patients with advanced-stage NSCLC were enrolled onto a phase II selection trial evaluating sequential or concurrent chemotherapy (paclitaxel plus carboplatin) with cetuximab.

Results: EGFR FISH was assessable in 76 patients with available tumor tissue and classified as positive (four or more gene copies per cell in >/= 40% of the cells or gene amplification) in 59.2%. Response (complete response/partial response) was numerically higher in FISH-positive (45%) versus FISH-negative (26%) patients (P = .14), whereas disease control rate (complete response/partial response plus stable disease) was statistically superior (81% v 55%, respectively; P = .02). Patients with FISH-positive tumors had a median progression-free survival time of 6 months compared with 3 months for FISH-negative patients (P = .0008). Median survival time was 15 months for the FISH-positive group compared with 7 months for patients who were FISH negative. (P = .04). Furthermore, survival favored FISH-positive patients receiving concurrent therapy.

Conclusion: These results are the first to suggest that EGFR FISH is a predictive factor for selection of NSCLC patients for cetuximab plus chemotherapy. Prospective validation of these findings is warranted.

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Figures

Fig 1
Fig 1
Phase II study design.
Fig 2
Fig 2
(A) Progression-free survival and (B) overall survival according to fluorescent in situ hybridization (FISH) status for the entire study population.
Fig 3
Fig 3
(A) Progression-free survival and (B) overall survival according to fluorescent in situ hybridization (FISH) status in concurrent treatment arm.
Fig 4
Fig 4
(A) Progression-free survival and (B) overall survival according to fluorescent in situ hybridization (FISH) status in sequential treatment arm.
See this image and copyright information in PMC

Comment in

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