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Clinical Trial
. 2010 Feb;5(2):169-78.
doi: 10.1097/JTO.0b013e3181c8cbd9.

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  1 , Ju-Whei Lee, Heinrich Roder, Julie Brahmer, Adriana Gonzalez, Joan H Schiller, David P Carbone
Affiliations
Clinical Trial

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 et al. J Thorac Oncol. 2010 Feb.

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.

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Figures

FIGURE 1
FIGURE 1
Kaplan-Meier analysis showing (A) overall survival and (B) time to progression for all analyzable patients.
FIGURE 2
FIGURE 2
Kaplan-Meier analysis showing (A) overall survival and (B) time to progression by exon 21 mutation.
FIGURE 3
FIGURE 3
Kaplan-Meier analysis showing (A) overall survival and (B) time to progression by KRAS mutation.
FIGURE 4
FIGURE 4
Kaplan-Meier analysis showing (A) overall survival and (B) time to progression as determined by matrix-assisted laser desorption ionization (MALDI).
See this image and copyright information in PMC

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