Balancing Safety and Efficacy of Epidermal Growth Factor Receptor Inhibitors in Patients With Squamous Cell Carcinoma of the Head and Neck

Iberri, David; Colevas, A. Dimitrios

doi:10.1634/theoncologist.2015-0177

Cited by 9 publications

(5 citation statements)

References 97 publications

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“…EGFR and human papillomavirus (HPV) are biomarkers that have been most extensively studied in HNSCCs. While EGFR overexpression has correlated with disease progression in HNSCC [ 5 , 6 , 25 ], EGFR expression status did not predicts clinical outcomes in the RTOG 0522 trial of concurrent accelerated RT plus cisplatin with or without cetuximab [ 9 ]. Prospective studies have reported that patients with HPV-positive metastatic HNSCC tended to benefit from the addition of anti-EGFR agents to chemotherapy [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

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The role of anti-EGFR agents in patients with locoregionally advanced head and neck cancer: a meta-analysis of randomized trials

et al. 2017

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There has been a debate over whether the addition of anti-epidermal growth factor receptor (EGFR) agents to the conventional treatments has beneficial effects in patients with head and neck squamous cell carcinoma (HNSCC). This meta-analysis was performed to investigate the role of anti-EGFR agents in patients with locoregionally advanced HNSCC (LA-HNSCC). A systematic search of the electronic databases was carried out. From eight randomized controlled trials, 2,263 patients were included in the meta-analysis. Compared with chemoradiotherapy (CRT), the addition of an EGFR inhibitor to radiotherapy (RT) or CRT did not improve locoregional control (hazard ratio (HR) = 1.19 [95% confidence interval (CI): 0.99–1.42], P = 0.06), progression-free survival (HR = 1.07 [95% CI: 0.92–1.24], P = 0.37), and overall survival (HR = 1.04 [95% CI, 0.88–1.23], P = 0.65) in patients with LA-HNSCC. Moreover, the addition of anti-EGFR agents increased the risk of skin toxicities (odds ratio = 4.04 [95% CI: 2.51–6.48], P < 0.00001) and mucositis (odds ratio = 1.58 [95% CI: 0.99–2.52], P = 0.06). In conclusion, this meta-analysis indicates that the addition of an anti-EGFR agent to RT or CRT do not improve clinical outcomes compared with CRT in patients with LA-HNSCC. Except for patients with coexisting medical conditions or decreased performance status, concurrent CRT should remain the standard of care for patients with LA-HNSCC.

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Section: Discussionmentioning

confidence: 99%

“…The epidermal growth factor receptor (EGFR) is expressed in about 80% of patients with HNSCC [ 5 ]. EGFR overexpression has been found to be an independent factor associated with unfavorable prognosis in these patients [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

The role of anti-EGFR agents in patients with locoregionally advanced head and neck cancer: a meta-analysis of randomized trials

et al. 2017

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“…For example, the EGFR inhibitor, gefitinib (Iressa), can enhance the apoptotic effects of cisplatin in SCC [17]. Clinical trials involving the combination regimens of anti-EGFR agents with immune checkpoint inhibitors are currently in progress for SCC of the head and neck [19,20]. In this study, we explored the role of Syk in EGFR signalling in three SCC cell lines (A431, CAL27, and SAS), analysed Syk expression in oral SCC cancer tissues, and determined the relationship between Syk activity and disease prognosis.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Anti-Tumour Effect of Syk Inhibitor and Olaparib in Squamous Cell Carcinoma: Roles of Syk in EGFR Signalling and PARP1 Activation

Huang

Chen

et al. 2020

Cancers

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Syk is a non-receptor tyrosine kinase involved in the signalling of immunoreceptors and growth factor receptors. Previously, we reported that Syk mediates epidermal growth factor receptor (EGFR) signalling and plays a negative role in the terminal differentiation of keratinocytes. To understand whether Syk is a potential therapeutic target of cancer cells, we further elucidated the role of Syk in disease progression of squamous cell carcinoma (SCC), which is highly associated with EGFR overactivation, and determined the combined effects of Syk and PARP1 inhibitors on SCC viability. We found that pharmacological inhibition of Syk could attenuate the EGF-induced phosphorylation of EGFR, JNK, p38 MAPK, STAT1, and STAT3 in A431, CAL27 and SAS cells. In addition, EGF could induce a Syk-dependent IL-8 gene and protein expression in SCC. Confocal microscopic data demonstrated the ability of the Syk inhibitor to change the subcellular distribution patterns of EGFR after EGF treatment in A431 and SAS cells. Moreover, according to Kaplan-Meier survival curve analysis, higher Syk expression is correlated with poorer patient survival rate and prognosis. Notably, both Syk and EGFR inhibitors could induce PARP activation, and synergistic cytotoxic actions were observed in SCC cells upon the combined treatment of the PARP1 inhibitor olaparib with Syk or the EGFR inhibitor. Collectively, we reported Syk as an important signalling molecule downstream of EGFR that plays crucial roles in SCC development. Combining Syk and PARP inhibition may represent an alternative therapeutic strategy for treating SCC.

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“…The epidermal growth factor receptor (EGFR) is a 170-kDa receptor tyrosine kinase expressed in epidermal tissues [4]. The high expression of EGFR -about ninety percent ** makes this target pivotal in HNSCC.…”

Section: Introductionmentioning

confidence: 99%

Maintenance Therapy with Biweekly Cetuximab: Optimizing Schedule Can Preserve Activity and Improves Compliance in Advanced Head and Neck Cancer

et al. 2018

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Objectives: This study evaluates maintenance cetuximab administered every 2 weeks (q2w) after chemotherapy plus cetuximab as first-line treatment in a series of patients with head and neck squamous cell cancer and compares the results with those obtained in a historical control group of patients receiving weekly cetuximab. Methods: After chemotherapy plus cetuximab as first-line treatment, in Group A, 36 patients enrolled from October 2016 to November 2017, received biweekly cetuximab, administered at 500 mg/m². Group B was a control group of patients treated at our institution from August 2015 to September 2016 and received weekly infusion of cetuximab at 250 mg/m². Results: Confirmed overall response rates were, respectively, 19% for Group A and 17% for Group B according to intention-to-treat analysis. During the maintenance treatment, median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 4.8 and 4.4 months; OS, 9.0 and 7.9 months; in Groups A and B, respectively). The most common adverse events among treated subjects included fatigue, rash, and hypomagnesemia. Conclusion: Maintenance therapy with simplified biweekly cetuximab is a convenient, effective, and well-tolerated regimen in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

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Balancing Safety and Efficacy of Epidermal Growth Factor Receptor Inhibitors in Patients With Squamous Cell Carcinoma of the Head and Neck

Cited by 9 publications

References 97 publications

The role of anti-EGFR agents in patients with locoregionally advanced head and neck cancer: a meta-analysis of randomized trials

The role of anti-EGFR agents in patients with locoregionally advanced head and neck cancer: a meta-analysis of randomized trials

Synergistic Anti-Tumour Effect of Syk Inhibitor and Olaparib in Squamous Cell Carcinoma: Roles of Syk in EGFR Signalling and PARP1 Activation

Maintenance Therapy with Biweekly Cetuximab: Optimizing Schedule Can Preserve Activity and Improves Compliance in Advanced Head and Neck Cancer

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