We are analyzing https://link.springer.com/article/10.1007/s40264-018-0772-x.

Title:
Safety and Tolerability of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Oncology | Drug Safety
Description:
Tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) have dramatically improved progression-free survival in non-small-cell lung cancer (NSCLC) patients who carry sensitizing EGFR-activating mutations and in patients with breast and pancreatic cancers. However, EGFR-TKIs are associated with significant and disabling undesirable effects that adversely impact on quality of life and compliance. These effects include dermatological reactions, diarrhoea, hepatotoxicity, stomatitis, interstitial lung disease and ocular toxicity. Each individual EGFR-TKI is also associated with additional adverse effect(s) that are not shared widely by the other members of its class. Often, these effects call for dose reduction, treatment discontinuation or pharmacotherapeutic intervention. Since dermatological effects result from on-target effects on wild-type EGFR, rash is often considered to be a biomarker of efficacy. A number of studies have reported better outcomes in patients with skin reactions compared with those without. This has led to a ‘dosing-to-rash’ strategy to optimize therapeutic outcomes. Although conceptually attractive, there is currently insufficient evidence-based support for this strategy. While skin reactions following EGFR-TKIs are believed to result from an effect on wild-type EGFR, their efficacy is related to effects on mutant variants of EGFR. It is noteworthy that newer EGFR-TKIs that spare wild-type EGFR are associated with fewer dermatological reactions. Furthermore, secondary mutations such as T790M in exon 20 often lead to development of resistance to the clinical activity and efficacy of first- and second-generation EGFR-TKIs. This has stimulated the search for later-generations of EGFR-TKIs with the ability to overcome this resistance and with greater target selectivity to spare wild-type EGFR in expectations of an improved safety profile. However, available data reviewed herein indicate that not only are these newer agents associated with the aforementioned adverse effects typical of earlier agents, but they are also susceptible to resistance due to tertiary mutations, most frequently C797S. At least three later-generation EGFR-TKIs, canertinib, naquotinib and rociletinib, have been discontinued from further development in NSCLC following concerns about their safety and risk/benefit.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

Education
Health & Fitness
Science

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

No common CMS systems were detected on Link.springer.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month

Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
However, some sources were not loaded, we suggest to reload the page to get complete results.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Link.springer.com Make Money? {💸}

The income method remains a mystery to us.

Websites don't always need to be profitable; some serve as platforms for education or personal expression. Websites can serve multiple purposes. And this might be one of them. Link.springer.com might be making money, but it's not detectable how they're doing it.

Keywords {🔍}

pubmed, google, scholar, article, cancer, cas, lung, egfr, kinase, inhibitors, cell, oncol, nonsmall, tyrosine, central, patients, epidermal, growth, factor, clin, receptor, drug, shah, resistance, phase, rash, skin, study, nsclc, treatment, inhibitor, erlotinib, clinical, res, safety, efficacy, lee, liu, nonsmallcell, effects, zhang, management, wang, afatinib, med, acquired, rev, advanced, osimertinib, review,

Topics {✒️}

irreversible pan-erbb inhibitor gov/scripts/cder/daf/index curl=pages/medicines/landing/epar_search egfr mutant-specific inhibitor t790m-specific egfr inhibitor egfr-tyrosine kinase inhibitor month download article/chapter egfr-tyrosine kinase inhibitors ph-dependent drug–drug interactions mutant-selective egfr inhibitor egfrl858r/t790m/c797s resistance mutations drug-specific assessment reports small-cell lung carcinoma spare wild-type egfr related subjects anti-lung cancer therapies tyrosine kinase inhibitors tyrosine-kinase inhibitors egfr-mutant lung cancer small-cell lung cancer small-cell lung cancer small cell lung cancer egfr t790m/c797s/v948r gov/drugsatfda_docs/label/2017/208772lbl gov/drugsatfda_docs/label/2016/021743s025lbl erlotinib-related skin effects treatment-naïve egfr-mutant insufficient evidence-based support egfr kinase inhibitors single-center prospective study targeting egfrl858r/t790m egfr tki-targeted therapy generation egfr inhibitor severe osimertinib-induced hepatotoxicity interstitial lung disease generation egfr inhibitors toxic epidermal necrolysis egfr mutation-positive pharmacokinetic drug-drug interactions t790m-positive nsclc open-label study wild-type egfr drug-specific reviews mechanism-based cancer therapeutics metastatic nsclc related egfr t790m mutation untreated egfr-mutated advanced egfr kinase domain literature-based meta-analysis t790m-specific

Questions {❓}

Dosing to rash?
Hyperglycaemia induced by novel anticancer agents: an undesirable complication or a potential therapeutic opportunity?
New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong?

Schema {🗺️}

WebPage:
      mainEntity:
         headline:Safety and Tolerability of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Oncology
         description:Tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) have dramatically improved progression-free survival in non-small-cell lung cancer (NSCLC) patients who carry sensitizing EGFR-activating mutations and in patients with breast and pancreatic cancers. However, EGFR-TKIs are associated with significant and disabling undesirable effects that adversely impact on quality of life and compliance. These effects include dermatological reactions, diarrhoea, hepatotoxicity, stomatitis, interstitial lung disease and ocular toxicity. Each individual EGFR-TKI is also associated with additional adverse effect(s) that are not shared widely by the other members of its class. Often, these effects call for dose reduction, treatment discontinuation or pharmacotherapeutic intervention. Since dermatological effects result from on-target effects on wild-type EGFR, rash is often considered to be a biomarker of efficacy. A number of studies have reported better outcomes in patients with skin reactions compared with those without. This has led to a ‘dosing-to-rash’ strategy to optimize therapeutic outcomes. Although conceptually attractive, there is currently insufficient evidence-based support for this strategy. While skin reactions following EGFR-TKIs are believed to result from an effect on wild-type EGFR, their efficacy is related to effects on mutant variants of EGFR. It is noteworthy that newer EGFR-TKIs that spare wild-type EGFR are associated with fewer dermatological reactions. Furthermore, secondary mutations such as T790M in exon 20 often lead to development of resistance to the clinical activity and efficacy of first- and second-generation EGFR-TKIs. This has stimulated the search for later-generations of EGFR-TKIs with the ability to overcome this resistance and with greater target selectivity to spare wild-type EGFR in expectations of an improved safety profile. However, available data reviewed herein indicate that not only are these newer agents associated with the aforementioned adverse effects typical of earlier agents, but they are also susceptible to resistance due to tertiary mutations, most frequently C797S. At least three later-generation EGFR-TKIs, canertinib, naquotinib and rociletinib, have been discontinued from further development in NSCLC following concerns about their safety and risk/benefit.
         datePublished:2019-01-16T00:00:00Z
         dateModified:2019-01-16T00:00:00Z
         pageStart:181
         pageEnd:198
         sameAs:https://doi.org/10.1007/s40264-018-0772-x
         keywords:
            Drug Safety and Pharmacovigilance
            Pharmacology/Toxicology
         image:
         isPartOf:
            name:Drug Safety
            issn:
               1179-1942
               0114-5916
            volumeNumber:42
            type:
               Periodical
               PublicationVolume
         publisher:
            name:Springer International Publishing
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Rashmi R. Shah
               affiliation:
                     name:
                     address:
                        name:Gerrards Cross, UK
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
               name:Devron R. Shah
               affiliation:
                     name:
                     address:
                        name:Gerrards Cross, UK
                        type:PostalAddress
                     type:Organization
               type:Person
         isAccessibleForFree:
         hasPart:
            isAccessibleForFree:
            cssSelector:.main-content
            type:WebPageElement
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:Safety and Tolerability of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Oncology
      description:Tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) have dramatically improved progression-free survival in non-small-cell lung cancer (NSCLC) patients who carry sensitizing EGFR-activating mutations and in patients with breast and pancreatic cancers. However, EGFR-TKIs are associated with significant and disabling undesirable effects that adversely impact on quality of life and compliance. These effects include dermatological reactions, diarrhoea, hepatotoxicity, stomatitis, interstitial lung disease and ocular toxicity. Each individual EGFR-TKI is also associated with additional adverse effect(s) that are not shared widely by the other members of its class. Often, these effects call for dose reduction, treatment discontinuation or pharmacotherapeutic intervention. Since dermatological effects result from on-target effects on wild-type EGFR, rash is often considered to be a biomarker of efficacy. A number of studies have reported better outcomes in patients with skin reactions compared with those without. This has led to a ‘dosing-to-rash’ strategy to optimize therapeutic outcomes. Although conceptually attractive, there is currently insufficient evidence-based support for this strategy. While skin reactions following EGFR-TKIs are believed to result from an effect on wild-type EGFR, their efficacy is related to effects on mutant variants of EGFR. It is noteworthy that newer EGFR-TKIs that spare wild-type EGFR are associated with fewer dermatological reactions. Furthermore, secondary mutations such as T790M in exon 20 often lead to development of resistance to the clinical activity and efficacy of first- and second-generation EGFR-TKIs. This has stimulated the search for later-generations of EGFR-TKIs with the ability to overcome this resistance and with greater target selectivity to spare wild-type EGFR in expectations of an improved safety profile. However, available data reviewed herein indicate that not only are these newer agents associated with the aforementioned adverse effects typical of earlier agents, but they are also susceptible to resistance due to tertiary mutations, most frequently C797S. At least three later-generation EGFR-TKIs, canertinib, naquotinib and rociletinib, have been discontinued from further development in NSCLC following concerns about their safety and risk/benefit.
      datePublished:2019-01-16T00:00:00Z
      dateModified:2019-01-16T00:00:00Z
      pageStart:181
      pageEnd:198
      sameAs:https://doi.org/10.1007/s40264-018-0772-x
      keywords:
         Drug Safety and Pharmacovigilance
         Pharmacology/Toxicology
      image:
      isPartOf:
         name:Drug Safety
         issn:
            1179-1942
            0114-5916
         volumeNumber:42
         type:
            Periodical
            PublicationVolume
      publisher:
         name:Springer International Publishing
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Rashmi R. Shah
            affiliation:
                  name:
                  address:
                     name:Gerrards Cross, UK
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
            name:Devron R. Shah
            affiliation:
                  name:
                  address:
                     name:Gerrards Cross, UK
                     type:PostalAddress
                  type:Organization
            type:Person
      isAccessibleForFree:
      hasPart:
         isAccessibleForFree:
         cssSelector:.main-content
         type:WebPageElement
["Periodical","PublicationVolume"]:
      name:Drug Safety
      issn:
         1179-1942
         0114-5916
      volumeNumber:42
Organization:
      name:Springer International Publishing
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:
      address:
         name:Gerrards Cross, UK
         type:PostalAddress
      name:
      address:
         name:Gerrards Cross, UK
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Rashmi R. Shah
      affiliation:
            name:
            address:
               name:Gerrards Cross, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Devron R. Shah
      affiliation:
            name:
            address:
               name:Gerrards Cross, UK
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Gerrards Cross, UK
      name:Gerrards Cross, UK
WebPageElement:
      isAccessibleForFree:
      cssSelector:.main-content

External Links {🔗}(429)

Analytics and Tracking {📊}

Google Tag Manager

Libraries {📚}

Clipboard.js
Prism.js

CDN Services {📦}

Crossref

5.1s.

LINK . SPRINGER . COM {}