Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer in eastern cooperative oncology group 3503

Joseph M. Amann, Ju Whei Lee, Heinrich Roder, Julie Brahmer, Adriana Gonzalez, Joan H. Schiller, David P. Carbone

Research output: Contribution to journalArticle

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Abstract

INTRODUCTION:: Serum proteomics and mutations in the epidermal growth factor receptor (EGFR) and KRAS have been associated with benefit after therapy with EGFR-targeted therapies in non-small cell lung cancer, but all three have not been evaluated in any one study. HYPOTHESIS:: Pretreatment serum proteomics predicts survival in Western advanced non-small cell lung cancer patients with wild-type EGFR and independent of KRAS mutation status. METHODS:: We analyzed available biospecimens from Eastern Cooperative Oncology Group 3503, a single-arm phase II study of erlotinib in first-line advanced lung cancer, for proteomics signatures in the previously described serum matrix-assisted laser desorption ionization proteomic classifier (VeriStrat) as well as for KRAS and EGFR mutations. RESULTS:: Out of 137 enrolled patients, analyzable biologic samples were available on 102. Nine of 41 (22%) demonstrated KRAS mutations and 3 of 41 (7%) harbored EGFR mutations. VeriStrat classification identified 64 of 88 (73%) as predicted to have "good" and 24 of 88 (27%) predicted to have "poor" outcomes. A statistically significant correlation of VeriStrat status (p < 0.001) was found with survival. EGFR mutations, but not KRAS mutations, also correlated with survival. CONCLUSIONS:: The previously defined matrix-assisted laser desorption ionization predictor remains a potent and highly clinically significant predictor of survival after first-line treatment with erlotinib in patients with wild-type EGFR and independent of mutations in KRAS.

Original languageEnglish (US)
Pages (from-to)169-178
Number of pages10
JournalJournal of Thoracic Oncology
Volume5
Issue number2
DOIs
StatePublished - Feb 2010

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Non-Small Cell Lung Carcinoma
Proteomics
Epidermal Growth Factor Receptor
Mutation
Survival
Therapeutics
Lasers
Serum
Erlotinib Hydrochloride
Lung Neoplasms

Keywords

  • EGFR
  • Erlotinib
  • KRAS
  • Lung cancer
  • Proteomics

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer in eastern cooperative oncology group 3503. / Amann, Joseph M.; Lee, Ju Whei; Roder, Heinrich; Brahmer, Julie; Gonzalez, Adriana; Schiller, Joan H.; Carbone, David P.

In: Journal of Thoracic Oncology, Vol. 5, No. 2, 02.2010, p. 169-178.

Research output: Contribution to journalArticle

Amann, Joseph M. ; Lee, Ju Whei ; Roder, Heinrich ; Brahmer, Julie ; Gonzalez, Adriana ; Schiller, Joan H. ; Carbone, David P. / Genetic and proteomic features associated with survival after treatment with erlotinib in first-line therapy of non-small cell lung cancer in eastern cooperative oncology group 3503. In: Journal of Thoracic Oncology. 2010 ; Vol. 5, No. 2. pp. 169-178.
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AU - Brahmer, Julie

AU - Gonzalez, Adriana

AU - Schiller, Joan H.

AU - Carbone, David P.

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N2 - INTRODUCTION:: Serum proteomics and mutations in the epidermal growth factor receptor (EGFR) and KRAS have been associated with benefit after therapy with EGFR-targeted therapies in non-small cell lung cancer, but all three have not been evaluated in any one study. HYPOTHESIS:: Pretreatment serum proteomics predicts survival in Western advanced non-small cell lung cancer patients with wild-type EGFR and independent of KRAS mutation status. METHODS:: We analyzed available biospecimens from Eastern Cooperative Oncology Group 3503, a single-arm phase II study of erlotinib in first-line advanced lung cancer, for proteomics signatures in the previously described serum matrix-assisted laser desorption ionization proteomic classifier (VeriStrat) as well as for KRAS and EGFR mutations. RESULTS:: Out of 137 enrolled patients, analyzable biologic samples were available on 102. Nine of 41 (22%) demonstrated KRAS mutations and 3 of 41 (7%) harbored EGFR mutations. VeriStrat classification identified 64 of 88 (73%) as predicted to have "good" and 24 of 88 (27%) predicted to have "poor" outcomes. A statistically significant correlation of VeriStrat status (p < 0.001) was found with survival. EGFR mutations, but not KRAS mutations, also correlated with survival. CONCLUSIONS:: The previously defined matrix-assisted laser desorption ionization predictor remains a potent and highly clinically significant predictor of survival after first-line treatment with erlotinib in patients with wild-type EGFR and independent of mutations in KRAS.

AB - INTRODUCTION:: Serum proteomics and mutations in the epidermal growth factor receptor (EGFR) and KRAS have been associated with benefit after therapy with EGFR-targeted therapies in non-small cell lung cancer, but all three have not been evaluated in any one study. HYPOTHESIS:: Pretreatment serum proteomics predicts survival in Western advanced non-small cell lung cancer patients with wild-type EGFR and independent of KRAS mutation status. METHODS:: We analyzed available biospecimens from Eastern Cooperative Oncology Group 3503, a single-arm phase II study of erlotinib in first-line advanced lung cancer, for proteomics signatures in the previously described serum matrix-assisted laser desorption ionization proteomic classifier (VeriStrat) as well as for KRAS and EGFR mutations. RESULTS:: Out of 137 enrolled patients, analyzable biologic samples were available on 102. Nine of 41 (22%) demonstrated KRAS mutations and 3 of 41 (7%) harbored EGFR mutations. VeriStrat classification identified 64 of 88 (73%) as predicted to have "good" and 24 of 88 (27%) predicted to have "poor" outcomes. A statistically significant correlation of VeriStrat status (p < 0.001) was found with survival. EGFR mutations, but not KRAS mutations, also correlated with survival. CONCLUSIONS:: The previously defined matrix-assisted laser desorption ionization predictor remains a potent and highly clinically significant predictor of survival after first-line treatment with erlotinib in patients with wild-type EGFR and independent of mutations in KRAS.

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