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Routine EGFR Molecular Analysis in Non-Small-Cell Lung Cancer Patients is Feasible: Exons 18–21 Sequencing Results of 753 Patients and Subsequent Clinical Outcomes

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Abstract

Background

Epidermal growth factor receptor (EGFR)-targeting therapies dramatically modified the prognosis of stage 4 non-small-cell lung cancer. Sensitizing EGFR mutations are the best efficacy factor of these treatments. In 2006, the French National Cancer Institute launched a network of 28 centers for EGFR molecular analysis in routine practice. The aim of this retrospective study was to describe the results of routine EGFR analysis in one of these centers (Lyon University Hospital) and to assess outcomes in patients with the mutation.

Methods

EGFR mutations were analyzed for exons 18–21 by direct sequencing. The characteristics of each sample were retrospectively collected from the lab archives. Subsequent outcomes for patients harboring at least one mutation were retrospectively collected from each referring physician.

Results

During 1 year, 792 samples were analyzed, corresponding to 753 patients. A total of 133 mutations were diagnosed in 124 samples (15.7 %), corresponding to 121 patients. Most of them (77.4 %) were sensitizing mutations and were located in exons 19 and 21. Others were resistance mutations (8.3 %) or rare mutations (14.3 %) for which effects on tyrosine kinase inhibitor (TKI) sensitivity are unknown. The rate of indeterminate results (i.e., no sequencing of the entire exon 19 or 21) was 6.3 % (n = 50 samples). The only factor statistically associated with a risk of failure was sample from bone tissue: 13.7 % gave incomplete results (i.e., no whole sequencing of exons 18–21).

Conclusions

Eighty-five of the 121 patients with EGFR mutations were treated with TKI. There were no differences in progression free survival (PFS) according to the type of molecule (erlotinib or gefitinib) or to the line of prescription of TKI. By contrast, exon 18 sensitizing mutations showed a worse PFS than exon 19 or 21 mutations. Finally, dose reduction was significantly more frequent in the erlotinib group than in the gefitinib group.

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Conflict of interest

SC declares that he has received fees for consulting, attending a meeting, and conducting a lecture from Roche, Astra Zeneca, Lilly, Glaxo-Smith Kline, Chugai, Vitalaire, Air-Product; and also research grants were paid at his institution from Pfizer, Roche, Astra Zeneca, Lilly, Pierre-Fabre, Boeringher Ingelheim, Laidet, Chugai. Other authors have none to declare.

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Authors and Affiliations

  1. Service de pneumologie et oncologie thoracique, CH Lyon Sud, Hospices Civils de Lyon, Lyon, France

    Myriam Locatelli-Sanchez, Sébastien Couraud & Pierre-Jean Souquet

  2. Faculté de médecine Lyon Sud, Université Lyon 1, Oullins, France

    Myriam Locatelli-Sanchez, Sébastien Couraud & Pierre-Jean Souquet

  3. Service de pneumologie, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France

    Dominique Arpin

  4. Service de pneumologie, Hôpital de Valence, Valence, France

    Robert Riou

  5. Service d’anatomie et de cytologie pathologique, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France

    Pierre-Paul Bringuier

Authors
  1. Myriam Locatelli-Sanchez
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  2. Sébastien Couraud
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  3. Dominique Arpin
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Correspondence to Sébastien Couraud.

Electronic Supplementary Material

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Electronic supplementary material The online version of this article (doi: 10.1007/s00408-013-9482-2) contains supplementary material which is available to authorized users. (DOCX 14 kb)

Collaborators of This Study

Collaborators of This Study

Philippe Ardisson, Dominique Arpin, Aline Bajard, Dominique Beal-Ardisson, Denis Beaute, Jacques Berger, Elisabeth Biron, Christian Bonnamour, Marie-Laure Braud, Philippe Brun, Serge Cabuzel, Gérard Chatte, Vincent Cottin, Jérôme Dagognet, Sylvie Demolombe, Arlette Desira, Gilles Devouassoux, Nouredine Douissa, Bernard Duvert, Bénédicte Etienne-Mastroianni, Lionel Falchero, Eric Fauchon, Patrick Fournel, Nathalie Freymond, Cécile Garnier, Béatrice gentil, Etienne Giroux Le Prieur, Valérie Grangeon, Patrick Hyvernat, Stéphane Hominal, Zouhair Jaouali, Géraldine Raichon-Patru, Sébastien Larive, Geneviève Letanche, Aurore Mallet, Philippe Mallinger, Catherine Marichy, Yann Martinat, Bernard Montagnon, Alain Penet, Maurice Perol, Marielle Perrichon, Bernard Raphanel, Anne-Claire Ravel, Paul Rebattu, Marielle Roux, Léa Saban Roche, Bernard Sanjuan, Jean François Vidal, Michel Vincent, Alain Voloch.

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Locatelli-Sanchez, M., Couraud, S., Arpin, D. et al. Routine EGFR Molecular Analysis in Non-Small-Cell Lung Cancer Patients is Feasible: Exons 18–21 Sequencing Results of 753 Patients and Subsequent Clinical Outcomes. Lung 191, 491–499 (2013). https://doi.org/10.1007/s00408-013-9482-4

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  • DOI: https://doi.org/10.1007/s00408-013-9482-4

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