PURPOSE: To evaluate the prognostic and predictive significance of plasma levels of the epidermal growth factor receptor (EGFR) ligands, transforming growth factor α (TGF-α) and amphiregulin, in patients with non-small-cell lung cancer (NSCLC) enrolled in NCIC Clinical Trials Group BR.21 comparing erlotinib with placebo. PATIENTS AND METHODS: TGF-α and amphiregulin were assessed retrospectively by enzyme-linked immunosorbent assay from available prospectively collected baseline plasma samples in 565 of 731 BR.21 patients. Cutoff points were determined for both amphiregulin (low, <10 pg/mL; high, ≥10 pg/mL) and TGF-α (low, ≤12 pg/mL; high, >12 pg/mL) using a graphical method. Cox regression models were used to correlate biomarker data and baseline characteristics with outcomes including overall (OS) and progression-free survival (PFS). RESULTS: High TGF-α and amphiregulin were associated with poorer performance status (P=.06 and P<.0001, respectively) and no prior platinum therapy (P=.06 and P=.02, respectively). High amphiregulin was also associated with anemia (P=.001), increased lactate dehydrogenase (P=.03), ever-smokers (P=.04), and non-Asian ethnicity (P=.001). Patients on the placebo arm with high amphiregulin had poorer OS than patients with low amphiregulin (hazard ratio [HR]=1.88; 95% CI, 1.34 to 2.64; P=.0002), which remained significant in multivariate analysis. Amphiregulin levels did not predict for benefit from erlotinib (interaction P=.87). Conversely, TGF-α levels did not have prognostic significance, but high TGF-α predicted lack of benefit from erlotinib compared with low TGF-α (TGF-α low, OS HR=0.66; 95% CI, 0.54 to 0.81; P<.0001; high, OS HR=1.32; 95% CI, 0.73 to 2.39; P=.36; interaction P=.04). CONCLUSION: High baseline amphiregulin is a poor prognostic factor, whereas high baseline TGF-α predicts for lack of benefit from erlotinib in advanced NSCLC.
PURPOSE: To evaluate the prognostic and predictive significance of plasma levels of the epidermal growth factor receptor (EGFR) ligands, transforming growth factor α (TGF-α) and amphiregulin, in patients with non-small-cell lung cancer (NSCLC) enrolled in NCIC Clinical Trials Group BR.21 comparing erlotinib with placebo. PATIENTS AND METHODS: TGF-α and amphiregulin were assessed retrospectively by enzyme-linked immunosorbent assay from available prospectively collected baseline plasma samples in 565 of 731 BR.21 patients. Cutoff points were determined for both amphiregulin (low, <10 pg/mL; high, ≥10 pg/mL) and TGF-α (low, ≤12 pg/mL; high, >12 pg/mL) using a graphical method. Cox regression models were used to correlate biomarker data and baseline characteristics with outcomes including overall (OS) and progression-free survival (PFS). RESULTS: High TGF-α and amphiregulin were associated with poorer performance status (P=.06 and P<.0001, respectively) and no prior platinum therapy (P=.06 and P=.02, respectively). High amphiregulin was also associated with anemia (P=.001), increased lactate dehydrogenase (P=.03), ever-smokers (P=.04), and non-Asian ethnicity (P=.001). Patients on the placebo arm with high amphiregulin had poorer OS than patients with low amphiregulin (hazard ratio [HR]=1.88; 95% CI, 1.34 to 2.64; P=.0002), which remained significant in multivariate analysis. Amphiregulin levels did not predict for benefit from erlotinib (interaction P=.87). Conversely, TGF-α levels did not have prognostic significance, but high TGF-α predicted lack of benefit from erlotinib compared with low TGF-α (TGF-α low, OS HR=0.66; 95% CI, 0.54 to 0.81; P<.0001; high, OS HR=1.32; 95% CI, 0.73 to 2.39; P=.36; interaction P=.04). CONCLUSION: High baseline amphiregulin is a poor prognostic factor, whereas high baseline TGF-α predicts for lack of benefit from erlotinib in advanced NSCLC.
Authors: Ahmad A Tarhini; Imran Rafique; Theofanis Floros; Phu Tran; William E Gooding; Liza C Villaruz; Timothy F Burns; David M Friedland; Daniel P Petro; Mariya Farooqui; Jose Gomez-Garcia; Autumn Gaither-Davis; Sanja Dacic; Athanassios Argiris; Mark A Socinski; Laura P Stabile; Jill M Siegfried Journal: Cancer Date: 2017-05-04 Impact factor: 6.860
Authors: William F Pirl; Lara Traeger; Joseph A Greer; Heather Bemis; Emily Gallagher; Inga Lennes; Lecia Sequist; Rebecca Heist; Jennifer S Temel Journal: Oncologist Date: 2011-08-01
Authors: E Nievergall; J Reynolds; C H Kok; D B Watkins; M Biondo; S J Busfield; G Vairo; K Fuller; W N Erber; T Sadras; R Grose; D T Yeung; A F Lopez; D K Hiwase; T P Hughes; D L White Journal: Leukemia Date: 2016-02-22 Impact factor: 11.528
Authors: W Jeffrey Petty; Jennifer Laudadio; Lynsay Brautnick; James Lovato; Travis Dotson; Nathan P Streer; Kathryn E Weaver; Antonius A Miller Journal: Int J Oncol Date: 2013-10-03 Impact factor: 5.650