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S.A. Melemed

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    ORAL 32 - EGFR WT and MT Targeting (ID 144)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      ORAL32.05 - EGFR IHC and FISH Correlative Analyses (SQUIRE Trial): Necitumumab + Gemcitabine-Cisplatin vs Gemcitabine-Cisplatin in 1st-Line Squamous NSCLC (ID 2651)

      16:45 - 18:15  |  Author(s): S.A. Melemed

      • Abstract
      • Presentation
      • Slides

      SQUIRE, a randomized phase III study, demonstrated that the addition of necitumumab (N) (a second-generation, recombinant, human immunoglobulin G1 EGFR antibody) to gemcitabine-cisplatin (GC) improved overall survival (OS) in patients with stage IV squamous non-small cell lung cancer (NSCLC). Analyses of the relationship between efficacy and epidermal growth factor receptor (EGFR) protein expression using the immunohistochemistry (IHC) H-score=200 cut-point were previously reported (Thatcher et al. Lancet Onc, 2015; doi: 10.1016/S1470-2045(15)00021-2). Here we report additional exploratory analyses of the relationship with EGFR protein, as well as analyses of EGFR gene copy number.

      SQUIRE included mandatory tissue collection from archived tumor. EGFR protein expression was assessed by IHC in a central lab, using the Dako EGFR PharmDx kit. Analyses of the relationships between efficacy outcomes with EGFR across the range of protein levels were performed, using methodologies including subpopulation treatment effect pattern plot (STEPP) with a sliding window target size of 200 patients. An exploratory assessment of EGFR gene copy number gain was performed in tissue sections using fluorescence in situ hybridization (FISH) (J Clin Pathol; 2009;62(11):970-7). Efficacy outcomes were estimated using the Kaplan-Meier method and hazard ratios estimated using an un-stratified Cox model. .

      A total of 982 patients (89.8% of the ITT) had evaluable IHC assay results. The large majority of these patients (95.2%) had tumor samples expressing EGFR protein; only 4.8% had tumors without detectable EGFR protein (H-score=0). The STEPP analyses showed no consistent trend or obvious cut-point for the relationship between either OS or PFS with EGFR protein across the range of IHC values when comparing treatment arms. Archived tumor tissue with evaluable results for exploratory EGFR FISH analysis was available for 51.0% of patients (557 of 1093 ITT patients). Of these patients, 208 patients (37.3%) had increased EGFR gene copy number (FISH positive). A trend for greater necitumumab benefit was observed in EGFR FISH positive patients. Treatment HR (95% CI) for FISH positive and negative patients were 0.70 (0.52, 0.96) and 1.02 (0.80, 1.29) for OS, and 0.71 (0.52, 0.97) and 1.04 (0.82, 1.33) for PFS. However, the interaction of EGFR gene copy number gain with treatment was not statistically significant for either OS or PFS (p=0.066 and 0.057, respectively).

      The analysis of EGFR protein expression did not identify consistent trends related to efficacy outcomes across the range of IHC values. EGFR gene copy number gain showed a trend for a more favorable HR, but did not appear to be strongly predictive. However, both markers showed some evidence of potential trends that will be investigated further in future trials.

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