Continuing posts summarizing my highlights from the oral presentations from WCLC 2011.
The Biomarkers V presentation highlight (O39.01) was a retrospective analysis of the CALGB 30406 study looking at the impact of specific EGFR mutations on outcomes. CALGB 30406 was a prospective trial in never/light smokers, previously untreated patients with advanced lung adenocarcinoma randomized to receive erlotinib (ERL) or ERL plus carboplatin and paclitaxel (C/P) as first-line therapy. Patients with EGFR mutations had similar outcomes (RR, PFS, OS) in both arms of the study vs. EGFR-wild type patients but no significant difference was seen in outcomes in exon 19 deletion vs. L858R mutation, irregardless of treatment arm. Good evidence to address a certainly relevant question.
Recent studies have shown that NSCLC can be differentiated into "epithelial-like" and "mesenchymal-like" tumors based on gene expression and EMT biomarkers have been associated with erlotinib activity in both in vitro and clinical specimens. Increasing evidence also suggests that changes in DNA methylation also are associated with the phenotypic EMT transition in lung cancer cells. MO16.02, presented in the Biomarkers VII session, is a proof-of-principle study by Genentech researchers using an integrated genomics approach combining gene expression profiling and methylated DNA immunopecipitation (meDIP) to define phenotypic subsets of NSCLC by their DNA methylation patterns. They further developed quantitative methylation-specific PCR assays for 14 markers identified by meDIP and pyrosequencing assays for another 5 markers. They tested a panel of NSCLC cell lines with defined responses to erlotinib by these assays and showed good correlation with erlotinib activity or EL/ML status. This study showed the potential for using DNA methylation profiles in targeted therapy profiles. This seemed like a lot of fancy razzle-dazzle in this context and I'm unclear what it would really add in a practical sense; it seems to me most of the work on DNA methylation patterns in lung cancer has been focused on identifying markers for early diagnosis in serum.