7022 Background: A multicenter phase I/II study found that inhibition of VEGF and EGFR with the combination of bevacizumab and erlotinib had significant antitumor efficacy in NSCLC, including activity in some tumors without EGFR mutations. We undertook a pilot project to determine if Matrix-Assisted Laser Desorption/Ionization- Time of Flight Mass Spectrometry (MALDI-TOF MS) proteomic analysis of patient serum could determine a profile that predicts response to therapy. Methods: Pretreatment serum was available for 37 of 40 patients with advanced NSCLC treated with bevacizumab and erlotinib. Each serum sample was diluted in a saturated sinapinic acid matrix solution prior to randomized placement on 64-well gold plates. MALDI-TOF mass spectra were obtained with a Voyager-DE STR instrument (PerSeptive Biosystems) and were replicated 9 times for each sample. The raw spectra were calibrated, corrected for baseline, and normalized prior to analysis. A linear mixed effects model was fit to the normalized intensities at each m/z value to evaluate expression differences between responders and progressors, while accounting for replicate sample variability. Results: Among the 37 patients with pretreatment serum, there were 8 (22%) with a partial response (PR), 7 (19%) with progressive disease (PD), and 22 (59%) with stable disease (SD) for a median of 14 wks (range 6 - 50 wks). Of 9 tumors that were tested for EGFR mutation, 1 mutant was identified (in a PR) and 8 had wild-type receptors (including 2 patients with a PR). Usable spectra were obtained from 87% of the MALDI-TOF replicates and reproducibility was excellent. We found 14 distinct m/z regions (2–19 kDa) with different intensity distributions between PR and PD patients at a p<0.001 threshold. Similar patterns were seen for patients with short-term SD (<12 wks) and patients with PD. Conclusions: MALDI-TOF MS proteomic analysis of pretreatment serum was able to identify protein/peptide expression patterns that discriminated between responders and progressors on this novel regimen. Additional work is planned to validate these results in a prospective data set and to identify proteins involved. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech