Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2014
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.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
75 citing papers in PubMed, 133 citations in OpenAlex.
- Trial
- A Randomized Phase II Study of FOLFOX With or Without the MET Inhibitor Onartuzumab in Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction.The oncologist · 2016Trial
- Hinge-region Cys-to-Ser mutation enables homogeneous DAR6 anti-c-Met biparatopic ADCs with tolerable O-glycosylation.Antibody therapeutics · 2026Article
- Preclinical PET characterization of [EJNMMI research · 2026Article
- ETV4 Promotes Colorectal Cancer Progression by Reprogramming Asparagine Metabolism to Remodel the Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immunological effects of amivantamab in EGFR or MET-expressing non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- MET Overexpression Is Associated with Superior Immunotherapy Benefit in Advanced Non-Small Cell Lung Cancer.Cancers · 2025Article
- MET (c-Met) protein overexpression is an emerging protein biomarker in non-small cell lung cancer.NPJ precision oncology · 2025Review
- A Phase II Study of Cabozantinib in Patients WithJTO clinical and research reports · 2025Article
- [Expert Consensus on Diagnosis and Treatment of NSCLC with MET Abnormalities (2025 Version)].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- MET overexpression correlated with prognosis of EGFR-mutant treatment‑naïve advanced lung adenocarcinoma: a real‑world retrospective study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Article
- Neoadjuvant Chemoimmunotherapy Increases Tumor Immune Lymphocytes Infiltration in Resectable Non-small Cell Lung Cancer.Annals of surgical oncology · 2023Article
- SYK-mediated epithelial cell state is associated with response to c-Met inhibitors in c-Met-overexpressing lung cancer.Signal transduction and targeted therapy · 2023Article
- The treatment of advanced non-small cell lung cancer harboring KRAS mutation: a new class of drugs for an old target-a narrative review.Translational lung cancer research · 2022Review
- Article
- A Biparatopic Antibody-Drug Conjugate to Treat MET-Expressing Cancers, Including Those that Are Unresponsive to MET Pathway Blockade.Molecular cancer therapeutics · 2021Article
- KRAS-Mutant Non-Small Cell Lung Cancer: An Emerging Promisingly Treatable Subgroup.Frontiers in oncology · 2021Review
- Selective Inhibitor of the c-Met Receptor Tyrosine Kinase in Advanced Hepatocellular Carcinoma: No Beneficial Effect With the Use of Tivantinib?Frontiers in immunology · 2021Review
- Current and future treatment options forTherapeutic advances in medical oncology · 2021Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeIn 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
designBiomarkers related to MET and/or EGF receptor (EGFR) signaling were measured by IHC, FISH, quantitative reverse transcription PCR, mutation detection techniques, and ELISA.
resultsA 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.
conclusionsMET IHC remains the most robust predictor of OS and progression-free survival benefit from O+E relative to all examined exploratory markers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.