Slight advantages of nimotuzumab versus cetuximab plus concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Wang, Jing; Yan, Weiwei; Liu, Yuguo; Ji, Li; Yu, Jinming; Zhu, Hui

doi:10.1080/15384047.2019.1598760

Cited by 19 publications

(13 citation statements)

References 32 publications

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“…Squamous cell carcinomas in the head and neck (HNSC), lung (LUSC), and esophagus (ESCA) have some commonalities: significantly increased EGFR expression, high frequency of EGFR amplification, and low rate of SNV/indel mutations. Targeted therapy with cetuximab or necitumumab (a monoclonal antibody targeting EGFR), along with radiotherapy or chemotherapy, have demonstrated promising efficacy and prolonged OS for locally advanced or recurrent and/or metastatic HNSC [54], ESCA [55‐57], and LUSC [58, 59], which is now a new first‐line treatment option in squamous NSCLC. The clear correlation between EGFR abnormal expression and treatment benefit highlights the importance of molecular profiling and predictive biomarkers for treatment selection.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan‐cancer analysis

Liu

Zhang

Sun

2020

Cancer Communications

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Background Human epidermal growth factor receptor (EGFR) is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR mutations. Although there are many reports for some individual cancers, comprehensive profiling of EGFR mutations, overexpression, amplification, DNA methylation, and their clinical associations across many different cancers simultaneously was not available. This study aimed to fill the gap and provide insights to the alteration spectrum of EGFR and its therapeutic and prognostic implications. Methods The Cancer Genome Atlas (TCGA) datasets for 32 cancer types involving 11,314 patients were analyzed for alterations (mutations and amplification/deletion), abnormal expression and DNA methylation in EGFR gene. Mutation frequency, genomic location distribution, functional impact, and clinical targeted therapy implication were compared among different cancer types, and their associations with patient survival were analyzed. Results EGFR alteration frequency, mutation sites across functional domains, amplification, overexpression, and DNA methylation patterns differed greatly among different cancer types. The overall mutation frequency in all cancers combined was relatively low. Targetable mutations, mainly in lung cancer, were primarily found in the Pkinase_Tyr domain. Glioblastoma multiforme had the highest rate of alterations, but it was dominated by gene amplification and most mutations were in the Furin‐like domain where targeted therapy was less effective. Low‐grade glioma often had gene amplification and increased EGFR expression which was associated with poor outcome. Colon and pancreatic adenocarcinoma had very few EGFR mutations; however, high EGFR expression was significantly associated with short patient survival. Squamous cell carcinoma regardless of their sites (the head and neck, lung, or esophagus) exhibited similar characteristics with an alteration frequency of about 5.0%, was dominated by gene amplification, and had increased EGFR expression generally associated with short patient survival. DNA methylation was highly associated with EGFR expression and patient outcomes in some cancers. Conclusions EGFR aberration type, frequency, distribution in functional domains, and expression vary from cancer to cancer. While mutations in the Pkinase_Tyr domain are more important for treatment selection, increased expression from amplification or deregulation affects more tumor types and leads to worse outcome, which calls for new treatment strategies for these EGFR‐driven tumors.

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Section: Discussionmentioning

confidence: 99%

Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan‐cancer analysis

Liu

Zhang

Sun

2020

Cancer Communications

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“…In this meta-analysis, there was no significant improvement in the PFS outcome in the anti-EGFR arm, which was consistent with the results of a previous meta-analysis. 52 A longer PFS was only confirmed for nimotuzumab combination therapy, as also reported by Jing et al 53 The biological characteristics of nimotuzumab differ from those of other anti-EGFR agents, which might explain its different clinical effects.…”

Section: Discussionmentioning

confidence: 54%

“… 52 A longer PFS was only confirmed for nimotuzumab combination therapy, as also reported by Jing et al . 53 The biological characteristics of nimotuzumab differ from those of other anti-EGFR agents, which might explain its different clinical effects.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of anti-epidermal growth factor receptor agents for the treatment of oesophageal cancer: a systematic review and meta-analysis

et al. 2021

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ObjectivesDespite remarkable advances in the treatment of oesophageal cancer (OC), the role of antiepidermal growth factor receptor (anti-EGFR) agents in treating OC remains controversial. Herein, a systematic review and meta-analysis were conducted to elucidate the efficacy and safety of anti-EGFR agents in patients with OC.DesignMeta-analysis of randomised controlled trials (RCTs) identified by searching the PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese Biology Medicine, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform databases from inception to December 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.SettingRCTs from any country and healthcare setting.ParticipantsPatients with OC.InterventionsCombination therapy with anti-EGFR agents and conventional treatments versus conventional treatments alone in patients with OC.Primary and secondary outcome measuresOverall survival (OS) and progression-free survival (PFS) were primary outcome measures, and objective response rate (ORR), disease control rate (DCR) and treatment toxicities were secondary outcome measures.ResultsIn total, 25 RCTs comprising 3406 patients with OC were included. Overall, anti-EGFR treatment significantly improved the OS (HR: 0.81, 95% CI 0.74 to 0.89, p<0.00001), ORR (relative risk (RR): 1.33, 95% CI 1.16 to 1.52, p<0.0001) and DCR (RR: 1.22, 95% CI 1.11 to 1.34, p<0.0001) but not PFS (HR: 0.91, 95% CI 0.76 to 1.08, p=0.26). Anti-EGFR treatment was significantly associated with higher incidences of myelosuppression, diarrhoea, acne-like rash and hypomagnesaemia.ConclusionsOverall, anti-EGFR agents have positive effects on OS, the ORR and DCR in OC. However, considering the high incidence of adverse effects, such as myelosuppression, diarrhoea, acne-like rashes and hypomagnesaemia, careful monitoring of patients with OC is recommended during anti-EGFR treatment.Trial registration numberCRD42020169230.

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“…It inhibits the EGFR-dependent intracellular signaling pathway via binding to the extracellular domain of EGFR ( Hirano and Kato, 2019 ). Many phase 2 clinical trials and retrospective studies had showed that in combination of nimotuzumab to chemotherapy or chemoradiotherapy could achieve effective benefits for advanced and metastatic ESCC ( Saumell et al, 2017 ; Jing et al, 2019 ). Pertuzumab is a humanized monoclonal HER2-targeted antibody which binds to a different epitope on the HER2 receptor protein than trastuzumab ( Shitara et al, 2020 ).…”

Section: Molecular Targeted Therapymentioning

confidence: 99%

Mechanisms of Pharmaceutical Therapy and Drug Resistance in Esophageal Cancer

Mao

Zeng

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Pharmaceutical therapies are essential for esophageal cancer (EC). For the advanced EC, the neoadjuvant therapy regimen, including chemotherapy plus radiotherapy and/or immunotherapy, is effective to achieve clinical benefit, even pathological complete response. For the unresectable, recurrent, and metastatic EC, the pharmaceutical therapy is the limited effective regimen to alleviate the disease and prolong the progression-free survival and overall survival. In this review, we focus on the pharmaceutical applications in EC treatment including cytotoxic agents, molecular targeted antibodies, and immune checkpoint inhibitors (ICIs). The chemotherapy regimen is based on cytotoxic agents such as platinum-based complexes, fluorinated pyrimidines and taxenes. Although the cytotoxic agents have been developed in past decades, the standard chemotherapy regimen is still the cisplatin and 5-FU or paclitaxel because the derived drugs have no significant advantages of overcoming the shortcomings of side effects and drug resistance. The targeted molecular therapy is an essential supplement for chemotherapy; however, there are only a few targeted therapies available in clinical practice. Trastuzumab and ramucirumab are the only two molecular therapy drugs which are approved by the US Food and Drug Administration to treat advanced and/or metastatic EC. Although the targeted therapy usually achieves effective benefits in the early stage therapy of EC, the patients will always develop drug resistance during treatment. ICIs have had a significant impact on routine clinical practice in cancer treatment. The anti-programmed cell death-1 monoclonal antibodies pembrolizumab and nivolumab, as the ICIs, are recommended for advanced EC by several clinical trials. However, the significant issues of pharmaceutical treatment are still the dose-limiting side effects and primary or secondary drug resistance. These defects of pharmaceutical therapy restrain the clinical application and diminish the effectiveness of treatment.

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Slight advantages of nimotuzumab versus cetuximab plus concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

Cited by 19 publications

References 32 publications

Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan‐cancer analysis

Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan‐cancer analysis

Efficacy and safety of anti-epidermal growth factor receptor agents for the treatment of oesophageal cancer: a systematic review and meta-analysis

Mechanisms of Pharmaceutical Therapy and Drug Resistance in Esophageal Cancer

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