Dataset Information

Biomarker analyses from a placebo-controlled phase II study evaluating erlotinib±onartuzumab in advanced non-small cell lung cancer: MET expression levels are predictive of patient benefit.

ABSTRACT:

Purpose

In a recent phase II study of onartuzumab (MetMAb), patients whose non-small cell lung cancer (NSCLC) tissue scored as positive for MET protein by immunohistochemistry (IHC) experienced a significant benefit with onartuzumab plus erlotinib (O+E) versus erlotinib. We describe development and validation of a standardized MET IHC assay and, retrospectively, evaluate multiple biomarkers as predictors of patient benefit.

Experimental design

Biomarkers related to MET and/or EGF receptor (EGFR) signaling were measured by IHC, FISH, quantitative reverse transcription PCR, mutation detection techniques, and ELISA.

Results

A positive correlation between IHC, Western blotting, and MET mRNA expression was observed in NSCLC cell lines/tissues. An IHC scoring system of MET expression taking proportional and intensity-based thresholds into consideration was applied in an analysis of the phase II study and resulted in the best differentiation of outcomes. Further analyses revealed a nonsignificant overall survival (OS) improvement with O+E in patients with high MET copy number (mean≥5 copies/cell by FISH); however, benefit was maintained in "MET IHC-positive"/MET FISH-negative patients (HR, 0.37; P=0.01). MET, EGFR, amphiregulin, epiregulin, or HGF mRNA expression did not predict a significant benefit with onartuzumab; a nonsignificant OS improvement was observed in patients with high tumor MET mRNA levels (HR, 0.59; P=0.23). Patients with low baseline plasma hepatocyte growth factor (HGF) exhibited an HR for OS of 0.519 (P=0.09) in favor of onartuzumab treatment.

Conclusions

MET IHC remains the most robust predictor of OS and progression-free survival benefit from O+E relative to all examined exploratory markers.

SUBMITTER: Koeppen H

PROVIDER: S-EPMC4504679 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Biomarker analyses from a placebo-controlled phase II study evaluating erlotinib±onartuzumab in advanced non-small cell lung cancer: MET expression levels are predictive of patient benefit.

Koeppen Hartmut H Yu Wei W Zha Jiping J Pandita Ajay A Penuel Elicia E Rangell Linda L Raja Rajiv R Mohan Sankar S Patel Rajesh R Desai Rupal R Fu Ling L Do An A Parab Vaishali V Xia Xiaoling X Januario Tom T Louie Sharianne G SG Filvaroff Ellen E Shames David S DS Wistuba Ignacio I Lipkind Marina M Huang Jenny J Lazarov Mirella M Ramakrishnan Vanitha V Amler Lukas L Phan See-Chun SC Patel Premal P Peterson Amy A Yauch Robert L RL

Clinical cancer research : an official journal of the American Association for Cancer Research 20140331 17

<h4>Purpose</h4>In a recent phase II study of onartuzumab (MetMAb), patients whose non-small cell lung cancer (NSCLC) tissue scored as positive for MET protein by immunohistochemistry (IHC) experienced a significant benefit with onartuzumab plus erlotinib (O+E) versus erlotinib. We describe development and validation of a standardized MET IHC assay and, retrospectively, evaluate multiple biomarkers as predictors of patient benefit.<h4>Experimental design</h4>Biomarkers related to MET and/or EGF ...[more]

PMID: 24687921

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Dataset Information

Biomarker analyses from a placebo-controlled phase II study evaluating erlotinib±onartuzumab in advanced non-small cell lung cancer: MET expression levels are predictive of patient benefit.

Purpose

Experimental design

Results

Conclusions

Publications

Biomarker analyses from a placebo-controlled phase II study evaluating erlotinib±onartuzumab in advanced non-small cell lung cancer: MET expression levels are predictive of patient benefit.

Similar Datasets

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