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M. Costantini

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    MINI 10 - ALK and EGFR (ID 105)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI10.01 - Frequency of Concomitant EGFR, EML4-ALK or KRAS Alterations in NSCLC Patients and Correlation with Response to Treatment (ID 942)

      16:45 - 18:15  |  Author(s): M. Costantini

      • Abstract
      • Presentation
      • Slides

      Epidermal growth factor receptor (EGFR) and KRAS mutations, and echinoderm microtubule-associated protein-like 4 (EML4) anaplastic lymphoma kinase (ALK) translocation are generally considered to be mutually exclusive. However, some reports show that a number of patients may have concomitant mutations, and it is not yet clear what impact these double mutations could have on response to targeted therapy.

      We took into consideration 380 NSCLC patients who underwent non-sequential testing for EGFR and KRAS mutations and EML4-ALK translocation between January 2010 and December 2013. EGFR mutation and EML4-ALK translocation analysis were performed on the entire case series and KRAS mutation analysis was performed on 282 cases.

      EGFR mutation and EML4-ALK translocation were present in 44 (11.6%) and 32 (8.4%) of patients, respectively. Ninety-two patients (32.6%) showed a KRAS mutation. Two concomitant mutations among EGFR, KRAS or EML4-ALK genes were observed in 16 patients. In particular, 6 of the 380 (1.6%) patients analyzed had concomitant EGFR mutation and EML4-ALK translocation. Of the 282 patients who also underwent KRAS mutation, 3 (1.1%) showed a concomitant EGFR and KRAS mutation and 7 (2.5%) a concomitant EML4-ALK and KRAS alteration. Of the 44 EGFR-mutated patients, 28 received a TKI-based treatment (24 with gefitinib and 4 with erlotinib) as first-line therapy, and 6 of these also had an EML4-ALK translocation. Among the 22 patients with EGFR mutation only, we observed 2 complete response (CR) (9%), 16 partial response (PR) (72.7%) and 4 progressive disease (PD) (18%). Of the 6 patients who also had an EML4-ALK translocation, one had CR (17%), 3 PR (50%) and 2 PD (33%). No differences were seen in terms of overall survival (OS). Of the 32 patients harboring the EML4-ALK translocation, 6 (those also carrying the EGFR mutation) were treated with a TKI as first-line therapy, while the others received chemotherapy. Twelve patients received crizotinib as second-line treatment and 7 progressed within 3 months of starting therapy. Of these, 2 showed a concomitant KRAS mutation (G12C) and one a concomitant EGFR mutation (exon 19 del). Two patients had stable disease, one of whom also showed a KRAS mutation (G12V). Two patients had PR and one had CR, all of whom showed a EML4-ALK translocation only. The median OS of the patients carrying an EML4-ALK translocation alone or a concomitant KRAS mutation was 57.1 (range 10.7-nr) and 10.7 (range 4.6-nr) months, respectively.

      The concomitant presence of EGFR, EML4-ALK or KRAS mutations is a possible event in NSCLC. KRAS mutation in patients with EML4-ALK translocation represents the most common double mutation and seems to confer a poor prognosis.

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