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T. Tanaka



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    P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P3.01-014 - Interleukin-6 Is a Valuable Predictive Marker for Therapeutic Effect of Gefitinib in Patients with Advanced NSCLC Harboring EGFR Mutations (ID 1187)

      09:30 - 09:30  |  Author(s): T. Tanaka

      • Abstract

      Background:
      Although epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitors (TKIs) are the key drug in patients with EGFR-mutant Non-small-cell Lung Cancer (NSCLC), some of them can not respond well to its therapy. An overexpression of Interleukin (IL)-6 in tumor cells is postulated as a potential mechanism for such resistance or low sensitivity to EGFR-TKI in the preclinical models (PNAS 2010). Here, we evaluated clinically if tumor IL-6 level can be predictive for the effect of EGFR-TKI therapy.

      Methods:
      A total of 52 patients with advanced EGFR-mutation NSCLC who had received gefitinib were retrospectively assessed. The protein expression of IL-6 in the tumor cells was immunostained. Each specimen was assessed independently by 2 physicians (YK and TT) and 2 pathologists (KI and TT), and judged as positive if ≥ 50% of 100 tumor cells were stained positively (BJC 1999). Serum IL-6 level was measured by CLEIA in 11 (21%) of 52 patients.

      Results:
      Patients demographics were as follows: 24 men; median age, 66 yrs; PS 0-1, 48; stage IV, 22; Ad, 49; exon19, 29). Of these, 24 (46%) and 28 (54%) were defined as IL-6-postitive (group P) and IL-6-negative (group N), respectively. Group P had worse PFS (75% v 92% at 6m; p < 0.05), which was retained in the multivariate analysis (HR: 2.38; 95%CI: 1.00-5.68; p=0.05) (Fig1). In contrast, PFS in the platinum-based chemotherapy did not differ in groups P and N (p=0.47). The serum IL-6 level ranged from 0.75 to 23.80 pg/ml (median: 2.90 pg/ml), which correlated neither to that in the tumor cells (regression coefficient: 1.69, p = 0.29) nor PFS in gefitinib therapy (p = 0.44). Figure 1 Figure 2





      Conclusion:
      Patients in group P benefited less from gefitinib therapy. This might suggest the inhibition of IL-6 expression can improve the low sensitivity to EGFR-TKI especially in EGFR-mutation tumors with high IL-6 expression.