Early PET analysis to identify responders to erlotinib treatment of advanced NSCLC.

Abstract

e18092 Background: EGFR mutations predict response to erlotinib treatment in advanced NSCLC. However, identification of EGFR mutations is not always possible due to lack of adequate tissue. We therefore investigated whether early PET might be a suitable tool to identify EGFR mutation positive responders. Methods: Six patients with NSCLC stage IIIB/IV showing partial remission according to RECIST criteria to first-line erlotinib treatment were analyzed and compared to 31 patients without response to first-line treatment with erlotinib. All patients were examined by [18F] FLT-PET and [18F] FDG-PET at baseline and after 1 week of treatment with erlotinib. The change in the sum of the maximum standard uptake value (sSUVmax) was calculated. Mutational status in each patient was analyzed by conventional Sanger sequencing. In case of negative results parallel sequencing using 454 technology was performed (EudraCT number 2005-005393-73; NCT00568841). Results: The median PFS for the 6 responding patients was 412 days. The mean reduction in the sSUV max was 37% (16-61) for [18F] FDG and 33% (0-55) for [18F] FLT after 1 week of treatment. Sanger sequencing of tissue available for molecular analyses revealed a sensitizing EGFR mutation in 3 of these 6 patients. Using the highly sensitve 454 technology an EGFR mutation could be demonstrated in 1 further patient. In the remaining two patients there was no diagnostic material allowing further molecular analyses. By comparison, the mean change in sSUVmax in patients not responding to erlotinib (n=31) was + 3% for [18F] FLT and -3% for [18F] FDG (p<0.005, T test). In the ROC analysis the AUC was calculated with 0.88 (0.73-1.00, p=0.004) for detection of response. Conclusions: Early [18F] FLT-PET and [18F] FDG-PET might be a suitable tool to detect patients with sensitizing EGFR mutations when treated with erlotinib. This might circumvent EGFR mutational analyses in patients with insufficient diagnostic material and enable early prediction of clinical response. Pat ID Histology Sanger 454 Change in sSUVmax LT-PET Change in sSUVmax FDPET 01-08 Adeno 0 del exon 19 -30 -44 01-18 Adeno del exon 19 N/A -44 -16 01-27 Adeno 0 N/A -55 -61 01-31 Adeno 0 N/A -39 -45 01-28 Adeno del exon 19 N/A 0 -38 01-25 Adeno L858R N/A -30 -22 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche