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Pathology & Oncology Research

, Volume 25, Issue 2, pp 513–520 | Cite as

Erlotinib for Patients with EGFR Wild-Type Metastatic NSCLC: a Retrospective Biomarkers Analysis

  • Alessandro InnoEmail author
  • Vincenzo Di Noia
  • Maurizio Martini
  • Ettore D’Argento
  • Mariantonietta Di Salvatore
  • Vincenzo Arena
  • Giovanni Schinzari
  • Armando Orlandi
  • Luigi Maria Larocca
  • Alessandra Cassano
  • Carlo Barone
Original Article
  • 93 Downloads

Abstract

Erlotinib is approved for the treatment of patients with EGFR mutation positive, metastatic NSCLC. It is also approved as second/third line therapy for EGFR mutation negative patients, but in this setting the benefit of erlotinib is modest and there is no validated biomarker for selecting EGFR wild-type patients who may benefit the most from the treatment. We retrospectively assessed EGFR and K-RAS mutational status, and EGFR, c-MET and IGF1-R expression in tumor samples of 72 patients with metastatic NSCLC treated with erlotinib after at least one prior line of chemotherapy, from 2008 to 2012. We analyzed the association between biomarkers and outcome (RR, PFS, and OS). EGFR mutated patients achieved a better RR (56% vs 8%, p = .002), PFS (10 vs 3 months, HR 0.53, p = 0.48) and OS (20 vs 6 months, HR 0.55, p = .07), compared to EGFR wild-type patients. Among 63 EGFR wild-type patients, those with EGFR high-expression had a better outcome in terms of RR (40% vs 2%, p = .002), PFS (7.5 vs 2 months, HR 0.45, p = .007) and OS (30 vs 5 months, HR 0.34, p < .001) compared to patients with EGFR intermediate or low/negative-expression. IGF1-R expression, c-MET expression and K-RAS mutational status did not significantly affect the outcome; however, no patients with K-RAS mutation or c-MET high-expression achieved an objective response. In patients with metastatic, chemo-refractory EGFR wild-type NSCLC, EGFR high-expression may represent a positive predictor of activity for erlotinib, whereas K-RAS mutation and c-MET high-expression may predict lack of activity. These findings deserve further prospective evaluation.

Keywords

EGFR wild-type NSCLC Erlotinib K-RAS mutation IGF1-R expression C-MET expression 

Notes

Compliance with Ethical Standards

Ethical Approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

For this type of study formal consent is not required.

Conflict of Interest

All authors declare that they do not have any conflict of interest.

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Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  • Alessandro Inno
    • 1
    Email author
  • Vincenzo Di Noia
    • 2
  • Maurizio Martini
    • 3
  • Ettore D’Argento
    • 2
  • Mariantonietta Di Salvatore
    • 2
  • Vincenzo Arena
    • 3
  • Giovanni Schinzari
    • 2
  • Armando Orlandi
    • 2
  • Luigi Maria Larocca
    • 3
  • Alessandra Cassano
    • 2
  • Carlo Barone
    • 2
  1. 1.Medical Oncology Unit, Cancer Care CenterOspedale Sacro Cuore Don CalabriaVeronaItaly
  2. 2.Department of Medical OncologyUniversità Cattolica del Sacro CuoreRomeItaly
  3. 3.Department of PathologyUniversità Cattolica del Sacro CuoreRomeItaly

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