<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>2184-0628</journal-id>
<journal-title><![CDATA[Gazeta Médica]]></journal-title>
<abbrev-journal-title><![CDATA[Gaz Med]]></abbrev-journal-title>
<issn>2184-0628</issn>
<publisher>
<publisher-name><![CDATA[Círculo Médico]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S2184-06282020000300263</article-id>
<article-id pub-id-type="doi">10.29315/gm.v7i3.337</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Recurrent and Metastatic Head and Neck Cancer: A Paradigm Shift?]]></article-title>
<article-title xml:lang="pt"><![CDATA[Cancro da Cabeça e Pescoço Recorrente/Metastático: Mudança de Paradigma?]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ribeiro]]></surname>
<given-names><![CDATA[Leonor Abreu]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Melo-Alvim]]></surname>
<given-names><![CDATA[Cecília]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Pais]]></surname>
<given-names><![CDATA[Helena Luna]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Costa]]></surname>
<given-names><![CDATA[Luís]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Serviço de Oncologia Médica, CHULN/HSM; Hospital CUF Infante Santo, Cluster Tejo, Instituto CUF Oncologia  ]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Serviço de Oncologia Médica, CHULN/HSM  ]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Instituto de Medicina Molecular Faculdade de Medicina de Lisboa ]]></institution>
<addr-line><![CDATA[Lisboa ]]></addr-line>
<country>Portugal</country>
</aff>
<pub-date pub-type="pub">
<day>30</day>
<month>09</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>30</day>
<month>09</month>
<year>2020</year>
</pub-date>
<volume>7</volume>
<numero>3</numero>
<fpage>263</fpage>
<lpage>269</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_arttext&amp;pid=S2184-06282020000300263&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_abstract&amp;pid=S2184-06282020000300263&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_pdf&amp;pid=S2184-06282020000300263&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract Head and neck squamous cell carcinoma (HNSCC), the most prevalent pathological subtype of head and neck carcinoma (HNC), can be potentially cured if diagnosed at early stages and adequately treated. Still, most patients are diagnosed at stages III or IV disease, with estimated local and distant failure rates of 60% and 30%, respectively, notwithstanding aggressive multimodality curative intent treatment strategies approved. The excellent results of the EXTREME trial published in 2008 showing a median overall survival (mOS), of 10.1 months for patients with recurrent and/or metastatic (R/M) HNSCC, treated with platinum plus fluorouracil (5FU) and cetuximab, changed the standard of care (SOC), for these patients. The EXTREME regime was the first to evidence an overall survival (OS) benefit before the immunotherapy era, in this context. Two immunotherapy drugs are currently approved for treatment of R/M HNSCC in first or subsequent lines of treatment both for platinum-resistant and platinum sensitive disease: the anti-PD-1 agents nivolumab and pembrolizumab. But does this mean that there is no longer a place for the EXTREME regimen or for chemotherapy in general in R/M HNSCC treatment? And if there is, how to choose between available therapeutic options? In this article, the authors will address these questions by analyzing data from the main trials that investigated nivolumab and pembrolizumab in this setting.]]></p></abstract>
<abstract abstract-type="short" xml:lang="pt"><p><![CDATA[Resumo O carcinoma pavimento celular (CPC), da cabeça e pescoço, o tipo histológico mais frequente do cancro da cabeça e pescoço, pode ser potencialmente curado se diagnosticado em estadios precoces e tratado adequadamente. Ainda assim, a maioria dos doentes são diagnosticados em estadio III ou IV da doença, com taxas de falência de resposta ao tratamento, local e à distância, de 60% e 30%, respetivamente, apesar de estratégias de tratamento multimodal com intenção curativa. Os excelentes resultados do ensaio EXTREME, publicado em 2008, com uma mediana de sobrevivência global de 10,1 meses dos doentes com CPC da cabeça e pescoço recorrente e/ou metastático tratados com platino associado a fluorouracilo e cetuximab, veio alterar o tratamento standard destes doentes. O regime EXTREME foi o primeiro esquema de tratamento a evidenciar um benefício em termos de sobrevivência global, antes da imunoterapia, neste contexto da doença. Os dois medicamentos de imunoterapia atualmente aprovados para o tratamento do CPC da cabeça e pescoço, em primeira ou subsequentes linhas de tratamento, para doença platino resistente e platino sensível são os agentes anti-PD-L1 nivolumab e pembrolizumab. Mas será que já não haverá lugar para o esquema EXTREME ou para a quimioterapia em geral para estes doentes? E se há, como escolher entre as opções terapêuticas existentes? Neste artigo, os autores irão, através da análise dos dados obtidos nos principais ensaios que investigaram o nivolumab e o pembrolizumab neste tipo de doentes, tentar responder a estas questões.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Head and Neck Neoplasms/tratamento farmacológico]]></kwd>
<kwd lng="en"><![CDATA[Neoplasm Recurrence, Local]]></kwd>
<kwd lng="en"><![CDATA[Nivolumab]]></kwd>
<kwd lng="en"><![CDATA[Pembrolizumab]]></kwd>
<kwd lng="pt"><![CDATA[Neoplasias da Cabeça e Pescoço/tratamento farmacológico]]></kwd>
<kwd lng="pt"><![CDATA[Nivolumab]]></kwd>
<kwd lng="pt"><![CDATA[Pembrolizumab]]></kwd>
<kwd lng="pt"><![CDATA[Recidiva Local de Neoplasia]]></kwd>
</kwd-group>
</article-meta>
</front><back>
<ref-list>
<ref id="B1">
<label>1</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Sacco]]></surname>
<given-names><![CDATA[AG]]></given-names>
</name>
<name>
<surname><![CDATA[Cohen]]></surname>
<given-names><![CDATA[EE]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Current treatment options for recurrent or metastatic head and neck squamous cell carcinoma]]></article-title>
<source><![CDATA[J Clin Oncol]]></source>
<year>2015</year>
<volume>33</volume>
<page-range>3305-13</page-range></nlm-citation>
</ref>
<ref id="B2">
<label>2</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Argiris]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Kramouzis]]></surname>
<given-names><![CDATA[MV]]></given-names>
</name>
<name>
<surname><![CDATA[Raben]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Ferris]]></surname>
<given-names><![CDATA[RL]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Head and neck cancer]]></article-title>
<source><![CDATA[Lancet]]></source>
<year>2008</year>
<volume>371</volume>
<page-range>1695-709</page-range></nlm-citation>
</ref>
<ref id="B3">
<label>3</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Seiwert]]></surname>
<given-names><![CDATA[TY]]></given-names>
</name>
<name>
<surname><![CDATA[Cohen]]></surname>
<given-names><![CDATA[EE]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[State-of-the-art management of locally advanced head and neck cancer]]></article-title>
<source><![CDATA[Br J Cancer]]></source>
<year>2005</year>
<volume>92</volume>
<page-range>1341-8</page-range></nlm-citation>
</ref>
<ref id="B4">
<label>4</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Vermorken]]></surname>
<given-names><![CDATA[JB]]></given-names>
</name>
<name>
<surname><![CDATA[Mesia]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Rivera]]></surname>
<given-names><![CDATA[F]]></given-names>
</name>
<name>
<surname><![CDATA[Remenar]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
<name>
<surname><![CDATA[Kawecki]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Rottey]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer]]></article-title>
<source><![CDATA[N Engl J Med]]></source>
<year>2008</year>
<volume>359</volume>
<page-range>1116-27</page-range></nlm-citation>
</ref>
<ref id="B5">
<label>5</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Mandal]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[&#350;enbabao&#287;lu]]></surname>
<given-names><![CDATA[Y]]></given-names>
</name>
<name>
<surname><![CDATA[Desrichard]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Havel]]></surname>
<given-names><![CDATA[JJ]]></given-names>
</name>
<name>
<surname><![CDATA[Dalin]]></surname>
<given-names><![CDATA[MG]]></given-names>
</name>
<name>
<surname><![CDATA[Riaz]]></surname>
<given-names><![CDATA[N]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[The head and neck cancer immune landscape and its immunotherapeutic implications]]></article-title>
<source><![CDATA[JCI Insight]]></source>
<year>2016</year>
<volume>1</volume>
</nlm-citation>
</ref>
<ref id="B6">
<label>6</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ferris]]></surname>
<given-names><![CDATA[RL]]></given-names>
</name>
<name>
<surname><![CDATA[Blumenschein Jr]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Fayette]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Guigay]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Colevas]]></surname>
<given-names><![CDATA[AD]]></given-names>
</name>
<name>
<surname><![CDATA[Licitra]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Nivolumab for recurrent squamous-cell carcinoma of the head and neck]]></article-title>
<source><![CDATA[New Engl J Med]]></source>
<year>2016</year>
<volume>375</volume>
<page-range>1856-67</page-range></nlm-citation>
</ref>
<ref id="B7">
<label>7</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Harrington]]></surname>
<given-names><![CDATA[KJ]]></given-names>
</name>
<name>
<surname><![CDATA[Ferris]]></surname>
<given-names><![CDATA[RL]]></given-names>
</name>
<name>
<surname><![CDATA[Blumenschein Jr]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Colevas]]></surname>
<given-names><![CDATA[AD]]></given-names>
</name>
<name>
<surname><![CDATA[Fayette]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Licitra]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Nivolumab versus standard, single-agent therapy of investigator&#8217;s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial]]></article-title>
<source><![CDATA[Lancet Oncol]]></source>
<year>2017</year>
<volume>18</volume>
<page-range>1104-15</page-range></nlm-citation>
</ref>
<ref id="B8">
<label>8</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Ferris]]></surname>
<given-names><![CDATA[RL]]></given-names>
</name>
<name>
<surname><![CDATA[Blumenschein Jr]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
<name>
<surname><![CDATA[Fayette]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Guigay]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Colevas]]></surname>
<given-names><![CDATA[AD]]></given-names>
</name>
<name>
<surname><![CDATA[Licitra]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Nivolumab vs investigator&#8217;s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression]]></article-title>
<source><![CDATA[Oral Oncol]]></source>
<year>2018</year>
<volume>81</volume>
<page-range>45-51</page-range></nlm-citation>
</ref>
<ref id="B9">
<label>9</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Cohen]]></surname>
<given-names><![CDATA[EW]]></given-names>
</name>
<name>
<surname><![CDATA[Soulières]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Le Tourneau]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<name>
<surname><![CDATA[Dinis]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Licitra]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Ahn]]></surname>
<given-names><![CDATA[MJ]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study]]></article-title>
<source><![CDATA[Lancet]]></source>
<year>2019</year>
<volume>393</volume>
<page-range>156-67</page-range></nlm-citation>
</ref>
<ref id="B10">
<label>10</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Mehra]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Seiwert]]></surname>
<given-names><![CDATA[TY]]></given-names>
</name>
<name>
<surname><![CDATA[Gupta]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Weiss]]></surname>
<given-names><![CDATA[J]]></given-names>
</name>
<name>
<surname><![CDATA[Gluck]]></surname>
<given-names><![CDATA[I]]></given-names>
</name>
<name>
<surname><![CDATA[Eder]]></surname>
<given-names><![CDATA[JP]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012]]></article-title>
<source><![CDATA[Br J Cancer]]></source>
<year>2018</year>
<volume>119</volume>
<page-range>153-9</page-range></nlm-citation>
</ref>
<ref id="B11">
<label>11</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Pai]]></surname>
<given-names><![CDATA[SI]]></given-names>
</name>
<name>
<surname><![CDATA[Faivre]]></surname>
<given-names><![CDATA[S]]></given-names>
</name>
<name>
<surname><![CDATA[Licitra]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Machiels]]></surname>
<given-names><![CDATA[JP]]></given-names>
</name>
<name>
<surname><![CDATA[Vermorken]]></surname>
<given-names><![CDATA[JB]]></given-names>
</name>
<name>
<surname><![CDATA[Bruzzi]]></surname>
<given-names><![CDATA[P]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040)]]></article-title>
<source><![CDATA[J Immunother Cancer]]></source>
<year>2019</year>
<volume>7</volume>
<page-range>96</page-range></nlm-citation>
</ref>
<ref id="B12">
<label>12</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Burtness]]></surname>
<given-names><![CDATA[B]]></given-names>
</name>
<name>
<surname><![CDATA[Harrington]]></surname>
<given-names><![CDATA[KJ]]></given-names>
</name>
<name>
<surname><![CDATA[Greil]]></surname>
<given-names><![CDATA[R]]></given-names>
</name>
<name>
<surname><![CDATA[Soulières]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Tahara]]></surname>
<given-names><![CDATA[M]]></given-names>
</name>
<name>
<surname><![CDATA[de Castro Jr]]></surname>
<given-names><![CDATA[G]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or me tastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study]]></article-title>
<source><![CDATA[TLancet]]></source>
<year>2019</year>
<volume>394</volume>
<page-range>1915-28</page-range></nlm-citation>
</ref>
<ref id="B13">
<label>13</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Rothschild]]></surname>
<given-names><![CDATA[U]]></given-names>
</name>
<name>
<surname><![CDATA[Muller]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<name>
<surname><![CDATA[Lechner]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<name>
<surname><![CDATA[Schlösser]]></surname>
<given-names><![CDATA[HA]]></given-names>
</name>
<name>
<surname><![CDATA[Beutner]]></surname>
<given-names><![CDATA[D]]></given-names>
</name>
<name>
<surname><![CDATA[Läubli]]></surname>
<given-names><![CDATA[H]]></given-names>
</name>
</person-group>
<article-title xml:lang=""><![CDATA[Immunotherapy in head and neck cancer -scientific rationale, current treatment options and future directions]]></article-title>
<source><![CDATA[Swiss Med Wkly]]></source>
<year>2018</year>
<volume>148</volume>
<page-range>w14625</page-range></nlm-citation>
</ref>
</ref-list>
</back>
</article>
