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Long-term clinical benefit from salvage EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer patients with EGFR wild-type tumors

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Abstract

Background

Erlotinib has been approved for the management of NSCLC patients after failure of the first or subsequent line of chemotherapy. Although the efficacy of erlotinib is clearly associated with the presence of EGFR mutations, there is a subset of patients with EGFR wild-type (EGFRwt) tumors who impressively respond.

Patients and methods

Patients with EGFRwt NSCLC who received salvage (≥2nd line) treatment with erlotinib for a prolonged period (>6 months), were sought from the database of the Hellenic Oncology Research Group. We retrospectively analyzed the clinical, pathological and molecular characteristics of the patients with available tumor material.

Results

Forty-four patients that received erlotinib for >6 months (median 10.1 months) were enrolled in the study. The majority of them were male, never-smokers with adenocarcinoma histology and a good performance status. KRAS and PIK3CA mutations were detected in 21% (9/42 tested) and 13% (4/30 tested) of the patients, respectively. The ALK-EML4 translocation was found in 10% (2/20 tested); there was no patient with HER2 or BRAF mutated tumor. Twelve (54.5%) tumor specimens were considered positive for EGFR-overexpression. Eleven patients experienced a partial response (objective response rate 25%; 95% CI 12–38%) and the remaining 33 had stable disease. The median progression-free survival and overall survival were 10.1 (95% CI 8.6–11.6 months) and 24.1 (95% CI 11.2–37 months), respectively.

Conclusions

Treatment with erlotinib significantly improves the clinical outcome in a subset of NSCLC patients with EGFRwt tumors. Further molecular analysis of such tumor specimens could provide a more comprehensive characterization of this particular group of patients. Nevertheless, the presence of other mutations should not prevent the treating physician from using erlotinib at later lines of salvage therapy for NSCLC patients.

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Acknowledgements

This work was financially supported by a research grant from the Cretan Association for Biomedical Research (CABR). We acknowledge the assistance of the scientific secretary Vasso Athanasaki in the preparation of this manuscript.

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  1. F. Koinis and A. Voutsina contributed equally.

Authors and Affiliations

  1. Department of Medical Oncology, University General Hospital of Heraklion, Voutes, P.O BOX 1352, 71110, Heraklion, Crete, Greece

    F. Koinis, E. K. Dermitzaki, E. Kontopodis, V. Georgoulias & A. Kotsakis

  2. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece

    A. Voutsina, A. Kalikaki, E. Tsakalaki, A. G. Pallis, V. Georgoulias & A. Kotsakis

  3. Department of Pathology, University General Hospital of Heraklion, Heraklion, Crete, Greece

    A. Koutsopoulos & E. Lagoudaki

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  1. F. Koinis
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Koinis, F., Voutsina, A., Kalikaki, A. et al. Long-term clinical benefit from salvage EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer patients with EGFR wild-type tumors. Clin Transl Oncol 20, 140–149 (2018). https://doi.org/10.1007/s12094-017-1702-6

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