Genomic Landscape of EGFR Mutant NSCLC Prior to Erlotinib and at the Time of Disease Progression

The investigators propose to conduct a pilot feasibility study of single agent erlotinib in
patients with metastatic EGFR mutant adenocarcinoma of the lung with up to one prior
treatment with the sole purpose of characterizing the genomic landscape before erlotinib and
at the time of disease progression. The logistics of obtaining adequate quality fresh tissue
specimens for sequencing studies before therapy and at the time of disease progression in
patients with advanced lung cancer are complex and a thorough understanding of the practical
challenges in conducting a study like this is crucial.

The current proposal will include exome and transcriptome sequencing from blood collected at
baseline along with tumor samples obtained prior to starting erlotinib and at the time of
disease progression (a total of two tissue samples and one blood sample per patient). If
carried out successfully, the proposed strategy very likely will lead to a larger and
adequately powered study to understand fully evolving molecular changes due to clonal
selection under treatment pressure. The pace of progress in the field of sequencing
technology currently underway is only likely to accelerate in the near future yielding richer
and highly content-rich information. Moreover, it is likely that genomic information from DNA
sequencing and transcriptome will be supplemented by analyses of translatomes and proteomes.

The investigators plan to sequence paired tumor specimens from 20 patients with EGFR mutant
adenocarcinoma of the lung before treatment with erlotinib and at the time of disease
progression following treatment with erlotinib. As the investigators expect some drop off
(due to unexpected clinical events precluding a second biopsy at the time of disease
progression, poor specimen quality and early discontinuation of therapy for non-progression),
the investigators will enroll 40 patients in this trial to get 20-paired specimens.