Table 1.

Predictive value of EGFR immunohistochemistry, EGFR, HER-2, and HER-3 gene copy numbers for response and survival in advanced NSCLC treated with EGFR TKIs

BiomarkerAuthor (reference)NDrug (dose, mg/d)Proportion positive (%)Response rates; positive vs. negativeSurvival hazard ratio (95% CI)
EGFR IHCCappuzzo (3)102Gefitinib (250)5921% vs. 5%0.60* (0.36-1.01)
EGFR IHCTsao (2)325Erlotinib (150)5711% vs. 4%0.68(0.49-0.95)
EGFR copy number by FISHCappuzzo (3)102Gefitinib (250)3236% vs. 3%0.44* (0.23-0.82)
EGFR copy number by FISHHirsch (4)82Gefitinib (500)3226% vs. 11%0.50 (0.25-0.97)
EGFR copy number by FISHTsao (2)125Erlotinib (150)4520% vs. 2%0.44§ (0.23-0.82)
EGFR copy number by FISHHirsch (17)352Gefitinib (250)3216% vs. 3%0.61 (0.36-1.04)
HER-2 copy number by FISHCappuzzo (18)102Gefitinib (250)2235% vs. 6%NR
HER-2 copy number by FISHHirsch (4)56Gefitinib (500)3036% vs. 46%NR
HER-3 copy number by FISHCappuzzo (20)82Gefitinib (250)2736% vs. 10%NR
EGFR copy number by qPCRBell (21)453Gefitinib (250 or 500)756% vs. 53%2.03 (0.67-6.13)
EGFR copy number by qPCRTakano (22)66Gefitinib (250)44OR, 4.6** (95% CI, 0.84-25)0.59* (0.26-1.4)
EGFR copy number by qPCRDziadziuszko(23)82Gefitinib (250)5112% vs. 10%1.04 (0.61-1.76)
  • NOTE: Unpublished studies on EGFR immunohistochemistry of Bailey et al.(15, 16) and from ISEL trial (9) are not included.

    Abbreviations: IHC, immunohistochemistry; NR, not reported.

  • * Comparison between positive and negative patients, multivariate analysis.

  • Comparison between erlotinib and placebo in immunohistochemistry-positive subgroup of patients, univariate analysis.

  • Comparison between positive and negative patients, univariate analysis.

  • § Comparison between erlotinib and placebo in FISH-positive subset of patients.

  • Comparison between gefitinib and placebo in FISH-positive or EGFR-amplified subset of patients.

  • Response rates to chemotherapy and gefitinib versus chemotherapy and placebo.

  • ** Odds ratio for response, indicating higher response probability in patients with high EGFR copy number.