Evaluation of Biomarkers for HER3-targeted Therapies in Cancer

摘要

Integration of biomarkers into the majority of drug developmentprograms has led to a need for robust measurements and assay validationtechniques for analyses of biological samples. The importance ofsolid methodologies for biomarker assessment is heightened by thefact that new drugs frequently only offer modest benefit and thatmany potential biomarkers are continuous variables, the application ofwhich relies on data interpretation, with the risk of subjectivity bias,to establish thresholds. Patritumab is a fully human anti-human epidermalgrowth factor receptor 3 (HER3) antibody that inhibits HER3 frombinding to HRG (Mendell et al., 2015). In the HERALD phase II trial,before data unblinding but after subject enrollment, heregulin (HRG)was prospectively declared to be the predictive biomarker forpatritumab efficacy. Advanced non-small cell lung cancer (NSCLC)patients previously treated with at least one chemotherapy regimenwere randomized to erlotinib plus patritumab (high- or low-dose) orerlotinib plus placebo (Mendell et al., 2015). Testing a single primarypredictive biomarker hypothesis to identify those patients most likelyto benefit from patritumab was a secondary objective of the trial andHRG was identified as a continuous biomarker to predict outcome.