When oral navitoclax (ABT-263) was evaluated in an open-label, phase 2 study in adult patients with recurrent and progressive small-cell lung cancer (SCLC) who had received at least 1 prior therapy, this Bcl-2 inhibitor showed only limited activity (Rudin CM, et al. Clin Cancer Res. 2012;18;1-7).
Nevertheless, this study provided evidence that selected biomarkers may have prognostic value in clinical settings; for example, the biomarker plasma pro–gastrin-releasing peptide (pro-GRP) may have value in predicting a patient’s potential to benefit from Bcl-2–directed therapy.
Efficacy end points included response rate, median progression-free survival (PFS), and median overall survival (OS). In addition, concentrations of several exploratory biomarkers, as well as tumor Bcl-2 gene copy numbers, were obtained in these patients and those from a related study.
Baseline concentrations of the biomarkers correlated with median PFS and median OS values. In addition, a strong association was demonstrated between pro-GRP concentration and tumor Bcl-2 copy number.
If confirmed, these study findings may have direct application to the implementation of future navitoclax studies, which the authors believe will focus on combination therapies.
