Validation of proteomic classifier for clinical benefit from erlotinib as first line treatment for advanced non-small cell lung cancer (ECOG 3503)

Abstract

7508 Background: In this study we tested the ability of our serum mass spectrometry classifier of clinical benefit from gefitinib to classify pre-treatment sera and plasma samples from non-small cell lung cancer (NSCLC) patients treated first line with erlotinib in ECOG E3503. Methods: Pretreatment serum and plasma samples were available from 73 of the 96 previously untreated advanced NSCLC patients treated with single agent erlotinib on ECOG protocol 3503, 13 subjects had only serum samples, and 10 had only plasma samples. All of these samples analyzed in replicate by MALDI mass spectrometry (MS). A prediction algorithm we established based on a training cohort of 139 patients treated second or third line with gefitinib was used to classify these patients for survival and time to progression, and results obtained from serum and plasma were compared when both were available Results: We found that the signals for the 8 distinct mass-to-charge (m/z) features used in our classifier were highly concordant between serum and plasma samples from the same patient, and that there was no difference in the classification of the patients between serum and plasma when both were available. Therefore we classified all 96 patients using serum if available, and plasma if not. The classification algorithm very successfully classified patients into groups with good and poor survival (median survival of 306 days vs 107 days, p = 0.0007). With the available follow-up, the time to progression was also statistically significant in this group (p = 0.007, data not shown). In a Cox multivariate analysis including the most significant univariate parameters PS (0 vs. 1 vs 2), number of involved sites (=3 vs >3) and prior weight loss (<5% vs = 5%), the MALDI MS classification algorithm retained independent significance at p = 0.03, with a hazard ratio of 0.53. Conclusions: This multi-institutional ECOG study demonstrates that MALDI MS can assist in the pre-treatment selection of a subgroup of NSCLC patients who are likely to show improved survival after treatment with first line erlotinib. No significant financial relationships to disclose.