Author of

• 10743

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  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10782

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    P1.10-039 - Characteristics of re-biopsied NSCLC patients with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (ID 2188)

    09:30 - 09:30  |  Author(s): K. Ishioka
    • Abstract

    Background
    Dramatic response of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) to non-small cell lung cancer (NSCLC) with activating EGFR mutations is known to be followed by subsequent resistance. Although various mechanisms of acquired resistance, such as EGFR secondary mutation (exon 20 T790M), the amplification of mesenchymal-epithelial transition factor, and hepatocyte growth factor overexpression have been reported, their frequency is not globally consistent. The purpose of this study is to retrospectively analyze the frequency of appearance of exon 20 T790M in re-biopsied specimens from NSCLC patients exhibiting acquired resistance to EGFR-TKIs.

    Methods
    We enrolled 16 patients who were treated with EGFR-TKIs after diagnosis of NSCLC with EGFR activating mutations and were re-biopsied after the resistance acquirement from January 2008 to December 2012 in Keio University hospital. Written informed consents were obtained from all the patients. We detected second mutations (exon 20 T790M) by PNA-LNA PCR clamp.

    Results
    The median (range) age of the patients was 59 (34-86) years, including 9 male and 7 female. Pathological diagnosis of primary tumors were adenocarcinoma for 14, mixed adenocarcinoma with small cell carcinoma for 1 and NSCLC-NOS for 1, with clinical staging stage IV for 13 and postoperative recurrence for 3 before starting EGFR-TKIs. Five patients were ex-smokers and 11 were non-smokers. Mutations of EGFR are exon 19 deletion for 7 patients, exon 21 L858R for 6, exon 21 L861Q for 2, and unspecified for 1. The median PFS was 306 days (95%CI: 97-514 days) with EGFR-TKIs (6 patients were treated with erlotinib and 10 patients were with gefitinib).For 11 patients, re-biopsy was performed during the treatment or within 2weeks of withdrawal of EGFR-TKIs. The specimens were obtained from primary sites in 6 patients and from metastatic sites in 5 (1 from cerebrospinal fluid, 1 from pleural effusion, 2 from lymph nodes and 1 from the skin). Pathological diagnosis was consistent to the original tumors for all cases, adenocarcinoma, except one with squamous cell carcinoma which was initially diagnosed as NSCLC-NOS. While all specimens remained original EGFR activating mutations, 3 out of 11 exhibited EGFR secondary mutation (exon 20 T790M).On the other hand, re-biopsy was performed long after discontinuation of EGFR-TKIs for 5 patients (median 6 months). All patients received subsequent chemotherapies after EGFR-TKIs. The specimens were taken from primary sites for 3 patients and from metastatic sites for 2 (1 from cerebrospinal fluid and 1 from lymph node). All specimens were adenocarcinoma as was so in initial diagnosis. All specimens kept original EGFR activating mutations, while 2 out of 5 exhibited EGFR secondary mutation (exon 20 T790M).

    Conclusion
    The frequency of exon 20 T790M in re-biopsied specimens was 27 % in NSCLC patients exhibiting acquired resistance to EGFR-TKIs (under or within 2 weeks after discontinuation of EGFR-TKIs). The other mechanisms behind the acquired resistance to EGFR-TKIs remain to be determined in this population.