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.

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.

sHRG level was various (−1346–11,772 pg/mL). Participants were divided into the sHRG-high or -low subgroups at the concentration defining near the third quartile, 980 pg/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.

sHRG seems to be a predictive biomarker for the efficacy of patritumab plus erlotinib in NSCLC patients.