3046 Impact of bevacizumab in combination with erlotinib on EGFRmutatant non-small cell lung cancer xenograft models with T790M mutation or MET amplification

Furugaki, Koh; Fukumura, Junko; Iwai, Takuma; Yorozu, Kensho; Yanagisawa, Mio; Moriya, Yoichiro; Kurasawa, Mitsue; Yamamoto, Kozo; Suda, Kenichi; Mizuuchi, Hiroshi; Mitsudomi, T.; Harada, Nobuhiro

doi:10.1016/s0959-8049(16)31688-4

Cited by 7 publications

(7 citation statements)

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“…Sakata et al found similar improved performance status and CSF penetration in one patient treated with this same combination. In this patient, CSF penetration of erlotinib was found to be 5.4%, much higher than the reported average CSF penetration of 1.13%±0.36% with erlotinib alone (12,21). Furugaki et al also found improvement in anti-tumor activity with the combination of bevacizumab to erlotinib, but only in the subset of patients with c-Met amplification and only in those who were already sensitive to erlotinib alone (22).…”

Section: ¹ X § Scontrasting

confidence: 52%

Targeted therapy for leptomeningeal metastases in non-small cell lung cancer – Changing treatment paradigms

Shah

Pak

Budhathoki

et al. 2017

Chinese Journal of Cancer Research

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Leptomeningeal metastasis is an uncommon but serious complication in patients with advanced cancers. Leptomeningeal metastasis is diagnosed in approximately 5% of the patients, most commonly among patients with cancers of breast and lung, melanoma, and gastrointestinal malignancies. Treatment goal is to improve survival and quality of the patients. Use of targeted therapies and immunotherapy has led to improved survival of patients with non-small cell lung cancer (NSCLC). In this article, we review emerging data on use of mutation-specific agents and immunotherapy in the treatment of leptomeningeal metastasis among patients with NSCLC.

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Section: ¹ X § Scontrasting

confidence: 52%

Targeted therapy for leptomeningeal metastases in non-small cell lung cancer – Changing treatment paradigms

Shah

Pak

Budhathoki

et al. 2017

Chinese Journal of Cancer Research

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“…14 In addition, in animal experiments, Furugaki et al confirmed that bevacizumab could enhance antitumor activity in T790M negative rather than in T790M positive tumors. 15 These results suggest that bevacizumab combined with chemotherapy is a better choice than chemotherapy alone in patients with non-T790M mutations who have experienced first-line EGFR-TKI failure.…”

Section: Discussionmentioning

confidence: 88%

Efficacy of pemetrexed and carboplatin with or without bevacizumab in lung adenocarcinoma patients with EGFR non‐T790M mutations after progression on first‐line EGFR‐tyrosine kinase inhibitors

et al. 2018

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BackgroundThe purpose of this study was to compare the effects of pemetrexed and carboplatin plus bevacizumab (PC + B) versus pemetrexed and carboplatin (PC) in lung adenocarcinoma patients with EGFR non‐T790M mutations after progression on first‐line EGFR‐tyrosine kinase inhibitors (TKIs).MethodsPatients with EGFR‐positive lung adenocarcinoma who had received second‐line PC with or without bevacizumab harboring EGFR non‐T790M mutations after progression on first‐line EGFR‐TKIs between April 2015 and 2017 at Tianjin Medical University Cancer Institute and Hospital were enrolled in the study. The primary endpoint was progression‐free survival and secondary endpoints were overall survival, objective response rate, disease control rate, and safety.ResultsA total of 85 patients were eligible for the study: 55 and 30 cases were enrolled in the PC and PC + B groups, respectively. The median progression‐free survival was prolonged with PC + B compared to PC (median 8.2 vs. 5.1 months; P = 0.037). The objective response rate was improved with PC + B compared to PC (46.7% vs. 25.5%; P = 0.047) and overall survival prolonged with PC + B compared to PC (median 26.3 vs. 19.2 months; P = 0.012). Safety was similar to previous studies of bevacizumab in non‐small cell lung cancer: one patient experienced grade 3 hypertension and proteinuria but did not require the discontinuation of therapy.ConclusionThe addition of bevacizumab to PC was superior to PC alone as second‐line therapy in patients with advanced non‐T90M EGFR‐positive lung adenocarcinoma. However, this result needs to be confirmed by prospective clinical trials.

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“…Combining other treatments with an antiangiogenic agent may prevent the development of an acquired resistance to EGFR-TKI, and may prolong the duration of the response. Although the mechanism responsible for the additional effect of EGFR-TKI and antiangiogenic agents have not been fully clarified, a recent in vivo study showed that using erlotinib in conjunction with bevacizumab enhanced antitumor activity in T790M mutation-positive or MET-amplified tumors as long as their growth remained significantly suppressed by erlotinib [37]. So far, no single theory can explain the mechanism of EGFR-TKI resistance system.…”

Section: Resultsmentioning

confidence: 99%

Progress toward resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitor

Zhang

Zhang²,

Zhao

2016

Open Life Sciences

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The EGFR signaling pathway plays an important role in the occurrence and development of many malignant tumors. It has become a hot spot in the treatment of advanced cancer. At present, the small molecule epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been shown to advanced non-small-cell lung cancer (NSCLC), has a marked drug resistance or has developed one. The EGFR signaling pathway regulates a variety of cellular functions, and its drug resistance may be related to a number of signal transduction pathways, including drug resistance mutations, structural activation, downstream signaling pathway activation and VEGF expression changes, and so on. In this paper, we review the production mechanism of EGFR-TKI drug resistance.

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3046 Impact of bevacizumab in combination with erlotinib on EGFRmutatant non-small cell lung cancer xenograft models with T790M mutation or MET amplification

Cited by 7 publications

References 0 publications

Targeted therapy for leptomeningeal metastases in non-small cell lung cancer – Changing treatment paradigms

Targeted therapy for leptomeningeal metastases in non-small cell lung cancer – Changing treatment paradigms

Efficacy of pemetrexed and carboplatin with or without bevacizumab in lung adenocarcinoma patients with EGFR non‐T790M mutations after progression on first‐line EGFR‐tyrosine kinase inhibitors

Progress toward resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitor

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