Epidermal Growth Factor Receptor (EGFR) co-mutated advanced non-small cell lung cancer (NSCLC) and response to EGFR tyrosine kinase inhibitors (TKIs) — ASN Events
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Epidermal Growth Factor Receptor (EGFR) co-mutated advanced non-small cell lung cancer (NSCLC) and response to EGFR tyrosine kinase inhibitors (TKIs) (#297)

Megan B. Barnet 1 2 , Sandra O'Toole 3 , Lisa` G. Horvath 1 2 , Christina Selinger 3 , Bing Yu 2 4 , Ronald Trent 2 , Chiu Chin Ng 4 , Michael J. Boyer 1 2 , Wendy Cooper 2 3 5 , Steven Kao 1 2
  1. Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia
  2. Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  3. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  4. Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  5. School of Medicine, University of Western Sydney, Parramatta, NSW, Australia

Background: Response to EGFR TKIs in NSCLC harbouring EGFR co-mutations is not well described. We aimed to examine the response rate to EGFR TKIs in a series of metastatic NSCLC patients with tumours harbouring EGFR mutation(s).

Methods: We reviewed mutation profiles of non-squamous NSCLC tested at Royal Prince Alfred Hospital from March 2012 to March 2014 by MassArray using OncoCarta v1.0 Panel.  Patients with metastatic disease whose tumours had EGFR mutation(s) were included and their clinical characteristics, treatment and outcome details were obtained and analysed.

Results: 245 tumours were profiled and an EGFR mutation was identified in 53 (22%) of these. 48 cases were metastatic, with 83% having common mutations (24 exon 21 L858R and 16 exon 19 deletions); some were co-mutated with either T790M substitution (n=2) or forms of PIK3CA mutation (n=3). 35 patients received initial treatment with a TKI (18 gefitinib, 14 erlotinib, 2 afatinib and 1 dacomitinib). 11 displayed either progressive or stable disease; which included both T790M substitutions, one PIK3CA co-mutation, five single L858R mutations, both single exon 18 mutations (G719A and E709K) and an exon 20 insertion mutation. 22 patients had partial (63%) and two had complete response (one exon 19 deletion and one L858R). Patients with an EGFR co-mutation tended to have lower response rates (40%) compared to those with a single EGFR mutation (80%), without reaching statistical significance (p=0.06).

Conclusion: Most patients with a single EGFR L858R or exon 19 deletion responded to treatment with a TKI. A proportion of tumours (10%) exhibited co-mutation with a resistant gene.  Taking into account the small number of patients included in this study, response rates in patients with co-mutations appeared low. More work is needed to define subgroups likely to display primary resistance to TKIs, who may benefit from an alternative first line therapy.

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