Clinical and biomarker outcomes of the phase II vandetanib study from the BATTLE trial.

Background: The Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination trial prospectively obtained serum and tumor core biopsies and randomized 255 chemorefractory non-small-cell lung cancer (NSCLC) patients into four phase II trials: erlotinib, erlotinib-bexarotene, vandetanib, or sorafenib. Herein, we report the clinical and biomarker results of the phase II vandetanib trial.

Results: Fifty-four patients received vandetanib. The 8-week disease control rate was 33%, median progression-free survival (PFS) 1.81 months, and median overall survival (OS) 6.5 months. No demographic subgroups had PFS or OS benefit. Eight patients with EGFR mutations had a trend for higher 8-week disease control rate (63% versus 31%; p = 0.12) but worse OS (5.9 months versus 9 months; p = 0.8). Patients with EGFR gene amplification (n = 6) had a worse OS (3.9 months versus 9.5 months; p = 0.04). KRAS mutation patients (3.9 months versus 9.5 months; p = 0.23) also had a worse OS. For the serum biomarker analysis, patients with below the median serum expression of interleukin 9c (p = 0.019) and eotaxin (p = 0.007) had a shorter PFS. A trend toward a shorter PFS was also seen in patients with higher than the median neutrophil gelatinase-associated lipocalin (p = 0.079) and lower than the median TNF-related apoptosis-inducing ligand (p = 0.087).

Conclusion: Our trial results are largely consistent with the literature in unselected pretreated NSCLC patients. Although vandetanib improved median PFS in EGFR mutation patients with epidermal growth factor receptor tyrosine kinase inhibitor-resistance compared with EGFR wild-type, there was no OS advantage. Although vandetanib is no longer in development in NSCLC, identification of a molecular phenotype that responds to dual epidermal growth factor receptor and vascular endothelial growth factor receptor inhibition would contribute to the field.