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R. Daniels



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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-008 - High Proportion of Unusual EGFR Mutations in an Australian Population of Non-Squamous NSCLC (ID 935)

      09:30 - 09:30  |  Author(s): R. Daniels

      • Abstract

      Background
      EGFR mutations have previously been reported in 10-15% of non-squamous NSCLC in European populations. The rate of mutations and the proportion of mutations considered to be classical activating, known to confer resistance or unusual is yet to be determined in the Australian population. The influence of unusual mutations on disease progression is not yet clear.

      Methods
      We conducted a retrospective audit of cases of non-squamous NSCLC lung cancer presenting to two metropolitan multidisciplinary teams in Sydney, Australia. All had EGFR testing conducted between October 2010-March 2013. EGFR mutations were identified using PCR and DNA sequencing.

      Results
      134 patient samples were tested for EGFR mutation. Samples were obtained by surgical resection (n=50), FNA (n=31), Core Biopsy (n=31), pleural fluid aspirate (n=3) and EBUS FNA (19). Of these, 32 (24%) were positive for an EGFR mutation. 23/32 had classical activating mutations, with 16/32 Exon 19 deletions and 7/32 Exon 21 L858 substitutions. 4/32 had non-activating/resistance mutations, with 3 exon 20 insertions and 1 exon 20 T790M (L858 + T790M complex de novo mutation). The remaining 6/32 had unusual mutations (1 Exon 20 ala 767-Val769 duplication, 1 Exon 21 p. Pro848Leu, 2 Exon 18 p. G719x, 1 exon 20 S761, D770 insertion and 1 exon 20 deletion V774 insertion). 72 patients in the cohort were female. 8 were Asian, 8 were Pacific Islander, 1 was Indian and 15 were Caucasian. Smoking history was confirmed in all cases. 18/32 were non-smokers, 3/32 were Asian and 24/32 were female. Of the patients with EGFR mutation positive tumours, 16/32 received TKI as first-line therapy, 5/32 received TKI as second-line therapy, 6/32 did not receive TKI and 5/32 were lost to follow-up in other institutions. Of the 6 who did not receive TKI, 5 cases were early-stage treated surgically; the other case received palliative radiotherapy but co-morbidity prevented TKI therapy. Information regarding disease progression was available in 20/32 cases. Of these cases 11/20 had classical activating mutations, were treated with EGFR TKI and, to date have a mean (SD) progression free survival (PFS) of 315 (± 208) d. Those with other mutations had a PFS of 117 (±86) d. This difference was statistically significant at p<0.01(Mantel-Cox).

      Conclusion
      EGFR mutations occur more commonly in an Australian population of non-squamous NSCLC than previously reported in European populations. Most in this series have classical activating mutations. Almost one third of this series had a mutation other than classically activating and in all of these cases the PFS was significantly reduced. We report six unusual mutations of unclear clinical significance, which are also associated with poor PFS.