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Allele specific gains of EGFR predicts benefit from EGFR-TKI treatment for advanced non–small-cell

Date

20 Dec 2015

Session

Poster presentation 2

Presenters

Xin Zhang

Citation

Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532

Authors

X. Zhang1, Y. Hou2, L. Zhang1

Author affiliations

  • 1 Pulmonary Medicine, Zhongshan Hospital, Fudan University, 200032 - Shanghai/CN
  • 2 Pathology, Zhongshan Hospital, Fudan University, 200032 - Shanghai/CN
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Aim/Background

Our aim was to determine whether allele specific gains of epidermal growth factor receptor (EGFR) in tumors predicts benefit from treatment with EGFR–tyrosine kinase inhibitors (TKIs) for advanced non–small-cell lung cancer (NSCLC).

Methods

We studied 87 patients with EGFR mutation-positive NSCLC who were treated with an EGFR tyrosine kinase inhibitor. Then the following detection was performed: ①EGFR mutant allele (MA) copies, EGFR wild type allele (WA) copies as well as reference gene ZNF679 copies were quantified by PCR (dPCR) .②Fluorescence in situ hybridization (FISH) were used to analysis the EGFR gene amplification. The amplification ratio was defined as the value of mutant clones / ZNF679 clones. Among the FISH positive patient, the amplification ratio > 0.5 was defined as mutant allele specific gains (MASG); the amplification ratio <0.5 was defined as wide type allele specific gains (WASG). Patients enrolled in our study were routinely followed up, and the effect of TKI treatment was evaluated as well.

Results

Of 87 samples, 36 and 22 harbored MASG and WASG of EGFR, respectively; 29 were FISH negative. Median progression-free survival (PFS) was 19 months (95% CI, 16.2 to 21.7) and 11 months (95% CI, 8.3 to 13.9) in MASG group and WASG group, respectively (P < 0.001). However, there was not significant difference between median PFS of WASG group and FISH negative group (12months 95% CI, 8.9-15.1 months P = 0.455). The objective response rate (ORR) was 66.7% in MASG group, 51.7% in FISH negative group; which were better than the ORR (27.3%) in the WASG group (P < 0.001). Cox regression analysis identified EGFR ASG type (P = 0.016) as independent factor predicting clinical benefit from EGFR-TKI in patients with EGFR-mutated NSCLC.

Conclusions

This research proves that the type of EGFR amplicatiom can predict benefit from EGFR-TKI treatment for advanced NSCLC. MASG is a better predictor in EGFR-TKI treatment.

Clinical trial identification

This article plans published in 3 months

Disclosure

All authors have declared no conflicts of interest.

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