Circulating heregulin level is associated with the efficacy of patritumab combined with erlotinib in patients with non-small cell lung cancer

Abstract Objectives Patritumab is a fully human anti-human epidermal growth factor receptor 3 (HER3) antibody that blocks activation by its ligand, heregulin (HRG). Preclinical studies have demonstrated the efficacy of patritumab in aberrantly high HRG-expressing non-small cell lung cancer (NSCLC). In the phase II randomized, placebo-controlled double-blind study HERALD ( n =212 patients with NSCLC), patritumab plus erlotinib did not improve progression-free survival (PFS) compared with placebo plus erlotinib. The current study examined whether soluble HRG (sHRG) level in serum correlated with the efficacy of patritumab plus erlotinib. Materials and methods Serum was obtained from participants prior to treatment ( n =202). sHRG level was measured using a validated quantitative immune assay, and correlations with survival were blindly assessed. Results sHRG level was various (−1346–11,772pg/mL). Participants were divided into the sHRG-high or -low subgroups at the concentration defining near the third quartile, 980pg/mL. Patritumab plus erlotinib significantly improved PFS relative to placebo in the sHRG-high subgroup ( n =46, hazard ratio 0.42 [0.19–0.96], p =0.0327). In contrast, the HRG-low subgroup ( n =148) had no improvement in PFS with patritumab. Conclusion sHRG seems to be a predictive biomarker for the efficacy of patritumab plus erlotinib in NSCLC patients.