7015 Background: Bronchioloalveolar carcinoma (BAC) and its variants are subtypes of pulmonary adenocarcinoma characterized by in situ growth along alveolar septae. We have previously shown (Franklin: ASCO, 2003) that BAC expresses both ErbB1 (EGFR) and ErbB2 (HER2) and exhibits activation of downstream signaling pathways reflected in phosphorylation of Akt and MAPK (Erk1/2). We hypothesized that biologic correlates of ErbB pathways in patient tumor tissue would predict benefit from Gefitinib in patients with BAC treated on S0126. Methods: Paraffin sections from 68 chemo-naïve and 31 previously treated patients were evaluated for the presence of tumor, cell type, grade, stromal invasion, mucin production, ErbB1, ErbB2, Ki-67, as well as pMAPK and pAKT, nuclear (N) and cytoplasmic (C). Each cell compartment was scored by two observers using the formula: % tumor cells positive (in 10% increments) X intensity of staining (0–4+ scale) = labeling score. Ki-67 was reported as percentage of tumor cells positive. Results: Pearson correlations (table) and survival analysis by Kaplan Meyer analysis in chemo-naïve patients are summarized below. There were significant correlations (**p<0.001) between ErbB2 and pMAPK (N and C), but not for ErbB1. There was a significant survival advantage for low (<=100) pMAPk N score (p=.02). A combination index of low ErbB2 (<=150) and low pMAPK(N) (<=100) also predicted better survival (p<0.01). ErbB1, pAKT and Ki-67 levels were not associated with outcome. Conclusions: 1) Low pMAPK(N) and combined low ErbB2 and pMAPK(N) predict increased survival with Gefitinib therapy in patients with advanced BAC. 2) These data suggest that dual inhibition of ErbB1 and ErbB2 may lead to improved therapeutic efficacy. 3) Correlations with histologic subtypes are ongoing. (CA32102, CA38926, CA58187) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca SWOG
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Franklin et al. (2004) studied this question.