MIMEB: A phase II trial to evaluate FDG-PET/FLT-PET, DCE-MRI and molecular biomarkers for early prediction of nonprogression in patients with advanced non-small cell lung cancer treated with erlotinib and bevacizumab.

e19049^ Background: Molecular imaging tools gain in importance for assessment of pharmacodynamics, pharmacokinetics, prognosis and prediction of therapeutic outcome in patients with advanced NSCLC treated with targeted therapy. We set up a prospective clinical trial in order to assess the predictive value of early changes in tumor metabolism (by FDG-PET), proliferation (by FLT-PET), and tumor vascularization (by DCE-MRI) noninvasively during therapy with erlotinib and bevacizumab in previously untreated patients with advanced non-squamous cell NSCLC. Methods: Patients with non-squamous NSCLC stage IV without prior systemic therapy received at least six weeks of combined erlotinib and bevacizumab. FLT and FDG-PET scans as well as DCE-MRI-scans were performed at baseline, after one week of therapy and after six weeks of therapy. Standard uptake values (SUVs) of the PET scans and vascularization parameters of the DCE-MRI scans were analyzed, coregistrated and compared with each other. The molecular markers were assessed using next-generation sequencing (NGS) and staining for an angiogenic phenotype. Results: Changes in FDG and FLT uptake after 1 week of therapy predicted nonprogression after 6 weeks of therapy with an area under the ROC curve of 0.75 (p=0.02) and 0.72 (p=0.045), respectively, in 38 evaluable patients. In 86% of the patients, ktrans in DCE-MRI showed a reduction after one week of therapy, while repeated baseline assessments showed reproducibility in a subset of patients. Beside patients with sensitizing EGFR mutations, clinical benefit could be seen in patients with PIK3CA, KRAS and ALK mutations. In these patients, both reduction of PET tracer uptake and ktrans in DCE-MRI could be detected. Conclusions: Imaging-based predictive biomarkers to identify the subpopulation of patients with pronounced benefit of the combination of erlotinib with bevacizumab were successfully added to the molecular-based selection of patients. Results of the ongoing analysis for evaluation of imaging analysis and correlation with tissue-based biomarkers will be presented. Clinical trial information: NCT01047059.