Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study.

Cunningham, David; Tebbutt, Niall C.; Давиденко, Ірина; Murad, André M.; Al‐Batran, Salah‐Eddin; Ilson, David H.; Tjulandin, Sergei; Gotovkin, Evgeny; Karaszewska, Bogusława; Bondarenko, Igor; Tejani, Mohamedtaki Abdulaziz; Udrea, Anghel Adrian; Tehfé, Mustapha; Baker, Nigel; Oliner, Kelly S.; Zhang, Yilong; Hoang, Tien; Sidhu, Roger; Catenacci, Daniel V.T.

doi:10.1200/jco.2015.33.15_suppl.4000

Cited by 107 publications

(88 citation statements)

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“…Notably, multiple phase III trials of agents aiming to target MET signaling have recently failed (5-7). However, the identification of oncogenic MET alterations in subsets of lung cancers has again led to increased interest in targeting this oncoprotein.…”

Section: Introductionmentioning

confidence: 99%

Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer

et al. 2016

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Amplified and/or mutated MET can act as both a primary oncogenic driver and as a promoter of tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). However, the landscape of MET-specific targeting agents remains underdeveloped and understanding of mechanisms of resistance to MET TKIs is limited. Here we present a case of a patient with lung adenocarcinoma harboring both a mutation in EGFR and an amplification of MET, who after progression on erlotinib, responded dramatically to combined MET and EGFR inhibition with savolitinib and osimertinib. When resistance developed to this combination, a new MET kinase domain mutation, D1228V, was detected. Our in vitro findings demonstrate that MET D1228V induces resistance to type I MET TKIs through impaired drug binding while sensitivity to type II MET TKIs is maintained. Based on these findings, the patient was treated with erlotinib combined with cabozantinib, a type II MET inhibitor, and exhibited a response.

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Section: Introductionmentioning

confidence: 99%

Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer

et al. 2016

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“…Despite solid preclinical evidence and promising phase 1/2 clinical trial results [43][44][45][46], several approaches to address RTK-related signaling pathways like EGFR, cMET/HGF, and mTOR failed in recent phase 3 studies [47][48][49][50][51]. This failure demonstrates our incomplete understanding of oncogenic pathways in gastric cancer.…”

Section: Growth Factor-related Signaling Pathways Beyond Her2mentioning

confidence: 84%

Insights into next developments in advanced gastric cancer

Obermannová

Lordick

2016

Current Opinion in Oncology

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“…In recent years, a series of large randomized Phase III trials of targeted therapy in nonbiomarker-selected patients have yielded negative results. These have included agents targeting the EGFR, MET, mTOR pathways [28][29][30][31][32]. This approach, in the absence of patient selection using validated biomarker associated with pathway activation, has clearly failed.…”

Section: Low Prevalence and Heterogeneous Biomarkers Require Smarter Trmentioning

confidence: 96%

Personalizing the Management of Gastroesophageal Cancer

Smyth

2015

Per. Med.

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Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study.

Cited by 107 publications

References 0 publications

Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer

Acquired METD1228V Mutation and Resistance to MET Inhibition in Lung Cancer

Insights into next developments in advanced gastric cancer

Personalizing the Management of Gastroesophageal Cancer

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