A window of opportunity study of potential tumor and soluble biomarkers of response to preoperative erlotinib in early stage non-small cell lung cancer
BACKGROUND: Erlotinib is highly active in EGFR mutant NSCLC, but may benefit some with wild-type tumors. We examined pre-operative erlotinib in early stage NSCLC to assess response and correlation with potential biomarkers.
RESULTS: Twenty-five patients were enrolled; 22 received erlotinib treatment and were evaluable (median follow-up 4.4 years). Histology was predominantly adenocarcinoma although 31% had squamous carcinoma. PET response was observed in 2 patients (9%), both with squamous carcinoma. Most (20/22) had stable disease (RECIST), with frequent minor radiographic regression and histologic findings of fibrosis/necrosis including in squamous histology. Only two had EGFR mutations identified, one with minor radiographic response and the other stable disease after 4 weeks of EGFR TKI. High pre-treatment serum levels of TGF-α correlated with primary resistance to erlotinib (p = 0.02), whereas high post-treatment soluble EGFR levels correlated with response (p = 0.03). EGFR, PTEN, cMET and AXL expression did not correlate with tumor response.
METHODS: Clinical stage IA-IIB NSCLC patients received erlotinib 150 mg daily for 4 weeks followed by resection. Tumor response was assessed using CT, PET and pathological response. Tumor genotype was established using Sequenom Mass ARRAY; EGFR, PTEN, cMET and AXL expression was assessed by immunohistochemistry, circulating markers of EGFR activation (TGF-α, amphiregulin, epiregulin, EGFR ECD) by ELISA and EGFR, MET copy number by FISH.
CONCLUSIONS: Erlotinib appears to demonstrate activity in EGFR wild-type tumors including squamous carcinoma. Further research is needed to characterize those wild-type patients that may benefit from EGFR TKI and predictive biomarkers including TGF-α, EGFR copy and others.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Oncotarget - 7(2016), 18 vom: 03. Mai, Seite 25632-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sacher, Adrian G [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 05.01.2018 Date Revised 13.11.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.18632/oncotarget.8350 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM25892313X |
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| 100 | 1 | |a Sacher, Adrian G |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A window of opportunity study of potential tumor and soluble biomarkers of response to preoperative erlotinib in early stage non-small cell lung cancer |
| 264 | 1 | |c 2016 | |
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| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Erlotinib is highly active in EGFR mutant NSCLC, but may benefit some with wild-type tumors. We examined pre-operative erlotinib in early stage NSCLC to assess response and correlation with potential biomarkers | ||
| 520 | |a RESULTS: Twenty-five patients were enrolled; 22 received erlotinib treatment and were evaluable (median follow-up 4.4 years). Histology was predominantly adenocarcinoma although 31% had squamous carcinoma. PET response was observed in 2 patients (9%), both with squamous carcinoma. Most (20/22) had stable disease (RECIST), with frequent minor radiographic regression and histologic findings of fibrosis/necrosis including in squamous histology. Only two had EGFR mutations identified, one with minor radiographic response and the other stable disease after 4 weeks of EGFR TKI. High pre-treatment serum levels of TGF-α correlated with primary resistance to erlotinib (p = 0.02), whereas high post-treatment soluble EGFR levels correlated with response (p = 0.03). EGFR, PTEN, cMET and AXL expression did not correlate with tumor response | ||
| 520 | |a METHODS: Clinical stage IA-IIB NSCLC patients received erlotinib 150 mg daily for 4 weeks followed by resection. Tumor response was assessed using CT, PET and pathological response. Tumor genotype was established using Sequenom Mass ARRAY; EGFR, PTEN, cMET and AXL expression was assessed by immunohistochemistry, circulating markers of EGFR activation (TGF-α, amphiregulin, epiregulin, EGFR ECD) by ELISA and EGFR, MET copy number by FISH | ||
| 520 | |a CONCLUSIONS: Erlotinib appears to demonstrate activity in EGFR wild-type tumors including squamous carcinoma. Further research is needed to characterize those wild-type patients that may benefit from EGFR TKI and predictive biomarkers including TGF-α, EGFR copy and others | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a erlotinib | |
| 650 | 4 | |a preoperative window study | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
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| 700 | 1 | |a Waddell, Thomas K |e verfasserin |4 aut | |
| 700 | 1 | |a Sakashita, Shingo |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhuo |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Lucia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Kamel-Reid, Suzanne |e verfasserin |4 aut | |
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| 700 | 1 | |a de Perrot, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Shepherd, Frances A |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Geoffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Tsao, Ming Sound |e verfasserin |4 aut | |
| 700 | 1 | |a Leighl, Natasha B |e verfasserin |4 aut | |
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