Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy
In lung cancer, several potential mechanisms of intrinsic and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been explored, including mesenchymal-epithelial transition factor (MET) signaling pathway activation. On the other hand, vascular endoth...
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doaj-a61b5c25b787476fbe1244205dda983b2020-11-24T21:57:44ZengKarger PublishersCase Reports in Oncology1662-65752019-01-01121919710.1159/000493088493088Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI TherapyNobuhiko SekiMaika NatsumeRyosuke OchiaiTerunobu HaruyamaMasashi IshiharaYoko FukasawaTakahiko SakamotoShigeru TanzawaRyo UsuiTakeshi HondaShuji OtaYasuko IchikawaKiyotaka WatanabeIn lung cancer, several potential mechanisms of intrinsic and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been explored, including mesenchymal-epithelial transition factor (MET) signaling pathway activation. On the other hand, vascular endothelial growth factor (VEGF) production of EGFR-mutated lung cancer cells is stimulated by predominantly activated MET signaling pathway. Therefore, the inhibition of VEGF axis as the downstream target of MET signaling pathway seems promising. Here, for the first time, we report the potential efficacy of combination therapy with bevacizumab and erlotinib in an EGFR-mutated NSCLC patient with MET amplification who showed intrinsic resistance to initial EGFR-TKI therapy. The patient was a 60-year-old male smoker, showing performance status (PS) 2, who presented with stage IV lung adenocarcinoma (cT4N2M1a) harboring the EGFR exon 19 deletion mutation. He was started on gefitinib at 250 mg/day. However, by 28 days, his symptoms further deteriorated along with the increased tumor size, resulting in PS 3. Then, repeat biopsy was performed, showing the positive MET amplification and the preserved EGFR exon 19 deletion mutation. Therefore, on the basis of the potential efficacy for activated MET signaling pathway as well as the confirmed safety by the known phase II trial for EGFR-mutated patients, the patient was started on combination therapy with bevacizumab at 15 mg/kg every 3 weeks plus erlotinib at 150 mg/day. By 21 days, his symptoms gradually improved along with the decreased tumor size, resulting in better PS with no severe toxicities.https://www.karger.com/Article/FullText/493088Lung cancerEGFR mutationMET amplificationErlotinibBevacizumab |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nobuhiko Seki Maika Natsume Ryosuke Ochiai Terunobu Haruyama Masashi Ishihara Yoko Fukasawa Takahiko Sakamoto Shigeru Tanzawa Ryo Usui Takeshi Honda Shuji Ota Yasuko Ichikawa Kiyotaka Watanabe |
spellingShingle |
Nobuhiko Seki Maika Natsume Ryosuke Ochiai Terunobu Haruyama Masashi Ishihara Yoko Fukasawa Takahiko Sakamoto Shigeru Tanzawa Ryo Usui Takeshi Honda Shuji Ota Yasuko Ichikawa Kiyotaka Watanabe Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy Case Reports in Oncology Lung cancer EGFR mutation MET amplification Erlotinib Bevacizumab |
author_facet |
Nobuhiko Seki Maika Natsume Ryosuke Ochiai Terunobu Haruyama Masashi Ishihara Yoko Fukasawa Takahiko Sakamoto Shigeru Tanzawa Ryo Usui Takeshi Honda Shuji Ota Yasuko Ichikawa Kiyotaka Watanabe |
author_sort |
Nobuhiko Seki |
title |
Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy |
title_short |
Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy |
title_full |
Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy |
title_fullStr |
Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy |
title_full_unstemmed |
Promising Combination Therapy with Bevacizumab and Erlotinib in an EGFR-Mutated NSCLC Patient with MET Amplification Who Showed Intrinsic Resistance to Initial EGFR-TKI Therapy |
title_sort |
promising combination therapy with bevacizumab and erlotinib in an egfr-mutated nsclc patient with met amplification who showed intrinsic resistance to initial egfr-tki therapy |
publisher |
Karger Publishers |
series |
Case Reports in Oncology |
issn |
1662-6575 |
publishDate |
2019-01-01 |
description |
In lung cancer, several potential mechanisms of intrinsic and acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been explored, including mesenchymal-epithelial transition factor (MET) signaling pathway activation. On the other hand, vascular endothelial growth factor (VEGF) production of EGFR-mutated lung cancer cells is stimulated by predominantly activated MET signaling pathway. Therefore, the inhibition of VEGF axis as the downstream target of MET signaling pathway seems promising. Here, for the first time, we report the potential efficacy of combination therapy with bevacizumab and erlotinib in an EGFR-mutated NSCLC patient with MET amplification who showed intrinsic resistance to initial EGFR-TKI therapy. The patient was a 60-year-old male smoker, showing performance status (PS) 2, who presented with stage IV lung adenocarcinoma (cT4N2M1a) harboring the EGFR exon 19 deletion mutation. He was started on gefitinib at 250 mg/day. However, by 28 days, his symptoms further deteriorated along with the increased tumor size, resulting in PS 3. Then, repeat biopsy was performed, showing the positive MET amplification and the preserved EGFR exon 19 deletion mutation. Therefore, on the basis of the potential efficacy for activated MET signaling pathway as well as the confirmed safety by the known phase II trial for EGFR-mutated patients, the patient was started on combination therapy with bevacizumab at 15 mg/kg every 3 weeks plus erlotinib at 150 mg/day. By 21 days, his symptoms gradually improved along with the decreased tumor size, resulting in better PS with no severe toxicities. |
topic |
Lung cancer EGFR mutation MET amplification Erlotinib Bevacizumab |
url |
https://www.karger.com/Article/FullText/493088 |
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