Prognostic value of c-MET in head and neck cancer: A systematic review and meta-analysis of aggregate data

Szturz, Petr; Budíková, Marie; Vermorken, Jan B.; Horová, Ivana; Gál, Břetislav; Raymond, Éric; Gramont, Armand de; Faivre, Sandrine

doi:10.1016/j.oraloncology.2017.09.009

Cited by 29 publications

(24 citation statements)

References 41 publications

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“…These results are consistent with other reports that EGFR inhibitors, including cetuximab, appear to be less active in patients with HPV‐positive/p16‐positive HNSCC . Comprehensive genomic analysis has revealed that EGFR gene amplification is common in HPV‐negative HNSCC but almost nonexistent in HPV‐positive HNSCC . This evidence suggests that patients with HPV‐positive HNSCC may not be a suitable population for anti‐EGFR therapies.…”

Section: Discussionsupporting

confidence: 91%

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

Kochanny

Worden

Adkins

et al. 2020

Cancer

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BACKGROUND: MET signaling is a well described mechanism of resistance to anti-EGFR therapy, and MET overexpression is common in head and neck squamous cell carcinomas (HNSCCs). In the current trial, the authors compared the oral MET inhibitor tivantinib (ARQ197) in combination with cetuximab (the TC arm) versus a control arm that received cetuximab monotherapy (C) in patients with recurrent/ metastatic HNSCC. METHODS: In total, 78 evaluable patients with cetuximab-naive, platinum-refractory HNSCC were enrolled, including 40 on the TC arm and 38 on the C arm (stratified by human papillomavirus [HPV] status). Patients received oral tivantinib 360 mg twice daily and intravenous cetuximab 500 mg/m 2 once every 2 weeks. The primary outcome was the response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), and secondary outcomes included progression-free and overall survival. After patients progressed on the C arm, tivantinib monotherapy was optional. RESULTS: The response rate was 7.5% in the TC arm (N = 3; 1 complete response) and 7.9% in the C arm (N = 3; not significantly different [NS]). The median progression-free survival in both arms was 4 months (NS), and the median overall survival was 8 months (NS). Both treatments were well tolerated, with a trend toward increased hematologic toxicities in the TC arm (12.5% had grade 3 leukopenia). The response rate in 31 HPV-positive/p16-positive patients was 0% in both arms, whereas the response rate in HPV-negative patients was 12.7% (12.5% in the TC arm and 13% in the C arm). Fifteen patients received tivantinib monotherapy, and no responses were observed. CONCLUSIONS: Combined tivantinib plus cetuximab does not significantly improve the response rate or survival compared with cetuximab alone but does increase toxicity in an unselected HNSCC population. Cetuximab responses appear to be limited to patients who have HPV-negative HNSCC. MET-aberration-focused trials for HNSCC and the use of higher potency, selective MET inhibitors remain of interest. Cancer 2020;126:2146-2152.We thank the patients and their families for their participation and the clinical and research staff at the participating institutions for their hard work. We also thank Shanda Lentz for her contributions while preparing the article. We thank the following faculty for their contributions to this trial and for entering their patients: : Data acquisition, statistical analysis, article preparation, and writing. Francis P. Worden: Patient enrollment. Douglas R. Adkins: Patient enrollment. Dean W. Lim: Patient enrollment. Julie E. Bauman: Patient enrollment. Stephanie A. Wagner: Patient enrollment. Ryan J. Brisson: Data acquisition and editing. Theodore G. Karrison: Formal statistical analysis. Walter M. Stadler: Trial management and advisor. Everett E. Vokes: Patient enrollment and methodology. Tanguy Y. Seiwert: Conceptualization, methodology, patient enrollment, article preparation, and writing.

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Section: Discussionsupporting

confidence: 91%

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

Kochanny

Worden

Adkins

et al. 2020

Cancer

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“…It has been widely shown in several in vitro and in vivo studies that HGF/Met signaling contributes to malignant properties in HNSCC [8]. Clinical data underscore that overexpression of HGF and/or Met results in shorter overall survival of HNSCC patients [4,6,7]. In contrast, in a phase 1/2 trial with foretinib, a Met-targeting tyrosine kinase inhibitor, the best response was only stable disease, and phase 2 was not entered (NCT00725764).…”

Section: Discussionmentioning

confidence: 99%

“…2020, 21, 471 2 of 17 of human tumor tissue samples and HNSCC cell lines [3]. Increased gene copy numbers or genetic mutations of Met are rather rare in HNSCC, so other mechanisms like transcriptional modulation could often be the cause for receptor overexpression [4]. Additionally, the ligand HGF was found to be overexpressed in almost 50% of human tumor tissue samples.…”

Section: Introductionmentioning

confidence: 99%

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The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma

Boschert

Klenk

Abt

et al. 2020

IJMS

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Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Methigh-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.

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“…It is towards the identification of biologic markers in cancer therapeutics that there is involved also paracrine/ autocrine stimulation of mesenchymal and vascular endothelial cell proliferation. Over-expression of c-Met is a common molecular finding in squamous cell carcinoma of the head and neck [6].…”

Section: Collaborative Attemptsmentioning

confidence: 99%

Attempts at Repeated Cell Re-Constitution as Integral Developmental Dynamics of Cell Proliferation in Oncogenesis

2018

Medical &Amp; Clinical Research

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Performance re-characterization of pathway definition constitutes the defining elements of patterned response of the injured integral cell that individually defines the nature of biology of the cell clone and of the specific transformation event in oncogenesis. Determining parameters concern the patterns of response in the face of ongoing oncogenesis in terms that elusively create an autonomous response as systems biology pathways. It is within the further cooperative patterns of single cell integrity that oncogenesis defines a determined focality of response in terms that overall defines the primal proliferation and scatter of cells as induced by hepatocyte growth factor/MET activation.

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Prognostic value of c-MET in head and neck cancer: A systematic review and meta-analysis of aggregate data

Cited by 29 publications

References 41 publications

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

A randomized phase 2 network trial of tivantinib plus cetuximab versus cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma

The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma

Attempts at Repeated Cell Re-Constitution as Integral Developmental Dynamics of Cell Proliferation in Oncogenesis

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