EGFR Gene Copy Number by FISH May Predict Outcome of Necitumumab in Squamous Lung Carcinomas: Analysis from the SQUIRE Study Article

International Collaboration

cited authors

  • Genova, Carlo, Socinski, Mark A., Hozak, Rebecca R., Mi, Gu, Kurek, Raffael, Shahidi, Javad, Paz-Ares, Luis, Thatcher, Nick, Rivard, Christopher J., Varella-Garcia, Marileila, Hirsch, Fred R.

funding text

  • Dr. Genova reports honoraria from AstraZeneca, Boehringer-Ingelheim, and Bristol-Myers Squibb. Drs. Hozak, Mi, and Kurek are employees and stockholders of Eli Lilly. Dr. Shahidi is former employee of Eli Lilly. Dr. Paz-Ares reports medical advisory fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, Roche, Novartis, Eli Lilly, and Pfizer. Dr. Thatcher reports speaker and board fees from Eli Lilly. Dr. VarellaGarcia reports a patent related to use of EGFR as a biomarker for electing therapy in lung cancer that is licensed to Abbott Molecular. Dr. Hirsch reports a patent related to use of EGFR as a biomarker for selecting therapy in lung cancer that is licensed to Abbott Molecular, as well as serving on advisory boards for Bristol-Myers Squibb, Genentech/Roche, HTG, Eli Lilly, Merck, Pfizer, and Ventana; in addition, Dr. Hirsch's laboratory has received research grants (through the University of Colorado) from Genentech, Bristol-Myers Squibb, Eli Lilly, Bayer, and Clovis. The remaining authors declare no conflict of interest.

abstract

  • Introduction: Necitumumab is a monoclonal antibody targeting EGFR. In the SQUIRE trial, the addition of necitumumab to chemotherapy for squamous cell lung cancer significantly improved overall survival (OS) (hazard ratio [HR] = 0.84); in a post hoc analysis, EGFR copy number gain determined by fluorescence in situ hybridization (FISH) showed a trend toward improved OS (HR = 0.70) and progression-free survival (PFS) (HR = 0.71) with the addition of necitumumab. We present the analysis of granular EGFR FISH data from SQUIRE to examine the potential predictive role of high polysomy and gene amplification, as both were included in the FISH-positive category. Methods: Available specimens from SQUIRE underwent FISH analysis in a central laboratory, and each sample was evaluated by using the Colorado EGFR scoring criteria. The correlation of granular FISH parameters with clinical outcomes was assessed. Results: Samples were available for 557 of 1093 patients; 208 patients (37.3%) were FISH-positive, including 167 (30.0%) with high polysomy and 41 (7.4%) with gene amplification. In patients with high polysomy, the addition of necitumumab resulted in a statistically significant increase in PFS (6.08 versus 5.13 months [p = 0.044]) and nonstatistically significant increase in OS (12.6 versus 9.5 months [p = 0.133]); among patients with gene amplification, the addition of necitumumab did not significantly improve PFS (7.4 versus 5.6 months; [p = 0.334]) but did improve OS (14.8 versus 7.6 months; [p = 0.033]). Conclusions: EGFR copy number gain by FISH might have a role as a predictive biomarker for necitumumab in squamous cell lung cancer. In our opinion, these data encourage further studies to prospectively evaluate this potential biomarker. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

authors

Publication Date

  • February 1, 2018

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published in

category

start page

  • 228

end page

  • 236

volume

  • 13

issue

  • 2

WoS Citations

  • 4

WoS References

  • 18