Molecular Imaging with C-11-PD153035 PET/CT Predicts Survival in Non-Small Cell Lung Cancer Treated with EGFR-TKI: A Pilot Study

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Abstract

Outcomes are suboptimal when molecularly targeted therapies are used in patient populations unselected for the molecular target. This pilot study examines the correlation of PET using (11)C-labeled 4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035), an imaging biomarker of epidermal growth factor receptor (EGFR), with outcomes in patients with non-small cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor erlotinib.Patients with advanced chemotherapy-refractory NSCLC were prospectively enrolled on a trial of erlotinib at a dose of 150 mg daily and imaged by (11)C-PD153035 PET/CT at baseline, after 1-2 wk, and after 6 wk from the start of treatment. Overall survival and progression-free survival (OS and PFS, respectively) times were correlated with the (11)C-PD153035 standardized uptake value (SUV) at each of the imaging times.Twenty-one patients were enrolled. Follow-up to progression was complete in all patients and to death in 18 of 21. By Cox regression analysis, baseline maximum SUV correlated strongly with OS and PFS (hazard ratio = 0.40, P = 0.002, and hazard ratio = 0.044, P < 0.001, respectively) independent of histology. Patients with higher maximum SUV (=median) survived more than twice as long as patients with lower maximum SUV (median OS = 11.4 vs. 4.6 mo, P = 0.002; PFS = 4.4 vs. 1.8 mo, P < 0.001). However, (11)C-PD153035 uptake on follow-up scans was less well correlated with survival.Our preliminary results suggest (11)C-PD153035 PET/CT may be a noninvasive and rapid method for identifying patients with refractory advanced NSCLC of adenocarcinoma or squamous histology likely to respond to the EGFR tyrosine kinase inhibitor but not for monitoring treatment response.

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