Author of

• 10801

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  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

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

  • 10831

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    P1.11-030 - Transaminitis induced by epidermal growth factor receptor tyrosine kinase inhibitor predicts for favourable outcome in EGFR mutation positive non-small cell lung cancer (ID 2203)

    09:30 - 09:30  |  Author(s): D.S.W. Tan
    • Abstract

    Background
    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are used as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) harbouring sensitizing mutations. Transaminitis is a known complication, and may impede the delivery of optimal doses of TKIs. We describe the incidence and severity of TKI induced transaminitis in patients with NSCLC treated with first line EGFR TKI and investigate its association with clinical outcomes. In addition, we review the management of patients who developed Grade 2/3 (G2/3) transaminitis or other TKI toxicity.

    Methods
    A retrospective study of 127 patients with EGFR mutation positive NSCLC treated at the National Cancer Centre Singapore with TKIs (gefitinib or erlotinib) over seven years (1/1/2006-30/5/2012) was conducted. Transaminitis was graded in accordance with CTCAE v4.0 criteria. Endpoints included dose adjustments, progression free survival (PFS) and overall survival (OS).

    Results
    Of 127 patients, 85 (66.9%) developed at least CTCAE v4.0 all grade transaminitis (G1/2/3: 75.3/11.8/12.9%) and 39 (30.7%) developed G1/2 bilirubin levels. No patients developed Grade 4 transaminitis. None had encephalopathy suggestive of fulminant liver failure. Median duration to onset of transaminitis was 1.87 months. Of 24 patients who had G2/3 transaminitis (n=21) or stopped TKI therapy due to other TKI toxicity (n=3), 8 switched to alternative regimen and/or therapies (alternative TKI only, n=3; alternative dosing schedule only, n=2; alternative dosing schedule followed by alternative TKI, n=2; switch to chemotherapy followed by alternative TKI, n=1). There was no change in TKI treatment and/or regimen for the other 16 patients. Development of transaminitis was independent of age, gender, smoking status and presence of brain metastases at baseline. Patients who developed transaminitis (all grades) had significantly longer PFS than those who did not (12.4 vs 8.2 months) (p=0.002). Patients with G1 ALT/AST had significantly longer PFS compared to G2/3 (G1/G2/G3: 13.4/3.0/11.9 months) (p=0.034). OS was not significantly affected by the presence and severity of transaminitis.

    Conclusion
    The incidence of EGFR TKI induced transaminitis in this cohort of patients appears higher than previously reported. Transaminitis, in particular G1, may be predictive of PFS for patients on TKIs. Patients should be monitored for the development of transaminitis, especially during the first two months of TKI treatment. Further studies are recommended to evaluate the role of transaminitis as a marker for TKI treatment efficacy.